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forms varying in the splicing of exons 6a, 10, 12, and 13. Genetic studies indicate that dysfunction in BIN1 is the second most important risk factor for AD. The mechanism through which BIN1 contributes to AD, though, is unclear. Studies suggest a range of possible reasons that BIN1 is associated with AD including interactions of BIN1 with the microtubule-associated proteins (i.e. CLIP170), endosomal trafficking of APP and APOE by BIN1, and BIN1 mediated regulation of inflammation through the expression of indoleamine 2,3-dioxygenase (IDO1). The interaction of BIN1 and tau might also be important because elevated levels of BIN1 are associated with increased AD risk through tau load; this result is suggested because of studies of the functional rs59335482 variant. Additionally, endocytic trafficking of APP by BIN1 could be important because trafficking determines if APP will undergo the non-amyloidogenic or the amyloidogenic pathway. For example, if APP is transported to the endosome, it will likely be cleaved by beta-secretase and undergo amyloidogenic processing, but if it accumulates on the cell surface it will be likely cleaved by alpha-secretase and undergo non-amyloidogenic processing. Lastly, BIN1 facilitates the kynurenine pathway of tryptophan metabolism by regulating the expression of the rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO1). For the IDO1 mechanism, increased BIN1 expression could increase levels of a toxic tryptophan derivative IDO1. These metabolites have been suggested to be involved in AD pathology and cognitive decline, as they co-localize with the plaques and NFTs in patient brains.
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dose of glucose. As with hypertension, diabetes is more common in the
Hispanic/Latino population than in the Caucasian population. In the U.S., Hispanic/Latinos are reported to have a diabetes prevalence of 22.6%, compared to 11.3% in non-Hispanic whites. This increased risk is associated with genetic factors, environmental factors (i.e. diet), and socioeconomic status. Recently AD has also been characterized as a metabolic disease of glucose regulation, as patients experience alterations in brain insulin responsiveness that leads to oxidative stress and inflammation. Changes in cerebral glucose signaling associated with AD have been proposed to as type three diabetes, although this has not been adopted as an official designation. Older diabetic Mexican Americans are twice as likely to develop dementia than those without diabetes. Additionally, the longer a patient is diabetic, the faster the rate of cognitive decline within the same and racial and age group.
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aggregation, which suggests that CLU has a neuroprotective effect. While one might expect AD to be associated with lower levels of a neuroprotective protein, biomarker studies indicate that CLU is upregulated in the plasma, CSF, hippocampus, and cortex of AD patients. One theory explaining this apparent contradiction is CLU is actually reduced early in life, increasing risk of developing AD. In this scenario, CLU might increase in subjects with AD as a compensatory response to the disease; further research is clearly necessary to clairy this area. However, genetic studies show that CLU is the third most significant risk factor for LOAD, which has propelled extensive genetic research related to CLU and AD. Two CLU variants of interest, that are associated with reduced AD frequency, are rs11136000 and rs9331896. However, little is known about the relationship between CLU and AD risk in the
Hispanic/Latino community.
103:. The National Institute of Health (NIH) reported that Hispanic and Latinos accounted for less than 8% of reported clinical trial participants. One proposed reason for the lack of representation is that the Hispanic/Latino population includes many people from different countries, and with this diverse background come different characteristics and comorbidities associated with AD. Hispanic and Latinos have a higher prevalence of AD compared to White non-Hispanics. Studies estimate that 12% of older Hispanic and Latino adults were diagnosed with AD, the highest proportion compared to all other ethnic groups. Hispanic and Latinos are the fastest-growing population in the U.S., and Hispanic/Latino seniors, those who are 65 and older, are expected to have the largest rise in AD and dementia cases compared to other populations, reaching 3.5 million by 2060. In 2011 the
528:. ABCA1 is a 220-240 kDa protein whose gene is located in chromosome 9q31.1 Its putative role in AD is tied to its role in stabilizing ApoE lipidation and degrading amyloid beta expressed in the brain. ABCA7 exhibits strong genetic linkage to AD; it is involved in lipid and cholesterol processing, as well as immune system function. ABCA7 exhibits tighter association with amyloid deposition than ABCA1. The research on ABCA7 mutations in the Hispanic/Latino population is a bit controversial. Some studies propose that mutations in ABCA7 are more common in Caucasian patients, whereas Hispanics/Latinos are more likely to express a BIN1 mutation. But researchers have still found polymorphisms specific to this population, one example being a 44-base pair frameshift deletion in
219:. TREM2 are highly expressed in microglia, the immune cell of the brain, tying the progression of AD with dysfunction in microglial activity. Neuroinflammation, Aβ and tau pathologies interact in Alzheimer's disease, and their progress can be monitored with biomarkers. For example, studies have found the neuroinflammatory marker YKL-40 in the cerebrospinal fluid (CSF) of AD patients. This protein increases years before the onset of AD symptoms and correlates with other neurodegenerative biomarkers, which suggests a potential to predict disease progression. While YKL-40 has not been shown to associate with the APOE -ε4 allele, there is research to link this biomarker to AD in the Hispanic population.
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only 45.6% of them were aware they had the condition. Hypertension is more apparent in the
Hispanic/Latino population, as in 2008 the incidence rate of hypertension for Hispanic adults aged 45–84 was 65.7%, compared to 56.8% for non-Hispanic whites of the same age. Hispanic/Latinos are more likely to be unaware of their condition, compared to non-Hispanics, and be less likely to seek treatment, which increases the risk of developing cardiovascular disease and AD. Hypertension can be reduced by lifestyle changes (e.g., weight loss and exercise) and pharmacological intervention. Multiple studies suggest that use of antihypertensive drugs might reduce the risk of dementia and AD.
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generation, Latinos over the age of 69, are fluent. Proficiency in
English is less of an issue for younger Latinos, with 90% of the population between the ages of 5 and 17 speaking the language fluently. Weak communication between physician and patient can also impair medical care. For instance, this issue occurs with clinical notes, which are typically translated from the English version of the same document for Spanish-speaking individuals. The medical community is attempting to address this issue by recruiting staff and physicians able to communicate with participants in their native language, as well as providing training on cultural sensitivity.
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trans-Golgi network. SORL1 plays an important role in the intracellular trafficking of APP. The protein can bind to APP expressed in endosomes and allow APP to be transported back to the cell surface, which prevents amyloidogenic processing and the production of cytotoxic Aβ40 and Aβ42. Moreover, SORL1 has been shown to facilitate cholesterol transport through its tendency to bind to APOE-lipoprotein complexes. Strong disease-linked polymorphisms in SORL1 combine with its role in APP trafficking render SORL1 a biomarker of strong interest for LOAD. Decreased levels of SORL1 transcript and protein have been observed in the brains of AD patients.
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68:
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literacy attained by
Hispanics and Latinos. As of 2013, it was reported that 22% of Latino adults (25 years and over) had earned an associate degree or higher, compared to the 46% seen in White Non-Hispanics. This trend is also seen with advanced degrees, as Latinos only account for 7% of Master's degrees and 1% Doctorate degrees awarded in the U.S. The lower measures of socioeconomic achievement and education level have been proposed to be associated with high mortality and dementia rates. In contrast, high educational levels are correlated with lower rates of dementia.
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435:
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developing AD. Genetic studies of
Hispanic and Latino populations, show a lower risk of developing AD for individuals with the APOE ε4 than observed in Caucasians. For instance, the prevalence of AD seen in Caribbean Hispanics, compared to White Non-Hispanics, appears to be independent of APOE genotype. Our understanding of ApoE ε4 continues to evolve, though, as Hispanic and Latino representation in research increases leading to larger sample sizes and improved population stratification .
55:(CLU) genes increasing one's risk to develop the condition. However, research has shown these high-risk genes have a different effect on Hispanics and Latinos then they do in other racial and ethnic groups. Additionally, this population experiences higher rates of comorbidities, that increase their risk of developing AD. Hispanics and Latinos also face socioeconomic and cultural factors, such as low income and a language barrier, that affect their ability to engage in
293:(NGRN). Due to the low use of CSF sampling in most countries, efforts have been made to study biomarkers in blood. Through work on blood biomarkers, researchers have been able to find proteins that are elevated in AD patients and have predictive potential. The predictive potential of these plasma markers increases further when coupled with the presence of genetic risk factors, such as the APOE E4 allele. Examples of plasma biomarkers include
457:, compared to amyloid beta-40. Unlike APOE4, PSEN1 mutations tend to have a clear pathological effect in Hispanics and Latinos and tend to express region-specific mutations. Puerto Ricans have a G206A mutation that causes familial AD, Cuban families diagnosed with EAOD commonly exhibit a L174M, mutation, Mexican families exhibit L171P and A431E mutations, and Colombian families exhibit an E280A mutation (particularly in the municipality of
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174:
237:
show that older
Hispanic/Latinos exhibit a higher prevalence of dementia than caucasians. Demographic and linguistic factors can prevent a proper MCI diagnosis. For instance, subjects for whom English might not be the primary language require use of a translator to perform the cognitive testing, which could affect testing results, but such experimental weaknesses are frequently not described.
241:
453:. The gene for PSEN1 is located on chromosome 14, q24.2, and consists of 12 exons that encode a 467-amino-acid protein that is predicted to traverse the membrane 9 times. Over 200 pathogenic mutations of this protein exist, many of which account for 18% to 50% of autosomal dominant EOAD cases. PSEN1 mutations increase the risk of developing AD by increasing the production of
257:(PET) is a brain imaging technique that uses a small amount of radioactive substance, called a tracer, to measure energy use or a specific molecule in different brain regions. In AD research, tracers can be used to detect neuritic plaques (containing Aβ) and tau. Depending on the tracer used, the signal can be used to determine the presence of neuritic plaques and NFTs.
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compared to
Caucasians. As of 2017, it has been reported that 35% of all Latinos suffer from an AD comorbidity, with 17% suffering from diabetes and 25.4% suffering from hypertension. The high prevalence of cardiovascular and metabolic conditions is thought to contribute to the higher risk of Alzheimer's Disease seen in Hispanics and Latinos
31:, that causes memory loss and cognitive decline in its patients. However, pathology and symptoms have been shown to manifest differently in Hispanic/Latinos, as different neuroinflammatory markers are expressed and cognitive decline is more pronounced. Additionally, there is a large genetic component of AD, with mutations in the
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124:(LOAD). EOAD is the less common of the two, accounting for 5-10%, and patients with EOAD are typically diagnosed with familial AD before they turn 65 years old. LOAD is more common and accounts for 90% of AD cases and its patients experience onset after they turn 65. EOAD has been shown to have 2 types of inheritance patterns:
639:
The term "Latino" denotes those who can trace their ancestry to Latin
America and the Caribbean. The diversity among Hispanic and Latino groups has led to proposals that the Latino/Hispanic population in the U.S. should not be treated as a homogenous group, and also to define subgroups based on their country of origin.
426:
91:. As of 2020, 5.4 million Americans have been diagnosed with Alzheimer's disease, and this number is projected to reach 15-22 million by 2050. Hispanics and Latinos account for 55 million of the population and this population is projected to rise to 97 million, accounting for 25% of the U.S. population, in 2050.
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Hispanic and
Latinos that are 65 years and older make up one of the largest groups of uninsured individuals in the U.S. This makes it difficult for these seniors to obtain the clinical care necessary for management of AD. The cost of care for insured patients 65 years and older was estimated to be $
638:
The terms Latino and Hispanic are used interchangeably in formal and informal settings. The term "Hispanic" specifically denotes those who can trace their ancestry to a Spanish-speaking country, such as Spain and most of Latin America, the exceptions being Brazil, Guyana, Suriname, and French Guiana.
469:
Bridging Integrator 1 (BIN1) is a widely expressed Bin-Amphiphysin-Rvs (BAR) adaptor protein that is located on chromosome 2, q14.3, and contains 20 exons. BIN1 mainly regulates clathrin-mediated endocytosis. Due to a large number of exons, this gene is subject to alternative splicing, with the major
182:
Neuritic plaques and neurofibrillary Tangles (NFTs) are the main pathological component of AD. Neuritic plaques are composed mainly of the peptide Aβ, but also include other components. APP is processed through either of two pathways, the first is termed the amyloidogenic pathway and produces Aβ. The
612:
is a metabolic condition characterized by high blood sugar and defective insulin secretion by pancreatic β-cells. A patient is diagnosed with diabetes when their fasting blood glucose levels are above 7.0 mmol/L (126 mg/dL) or above 11.1 mmol/L (200 mg/dl) two hours after an oral
540:
Clusterin (CLU), also known as apolipoprotein J, is an 82 kDa glycoprotein protein that is located on chromosome 8. It has multiple physiological functions, some examples being lipid transport, immune modulation, and cell death. CLU is known to have the ability to clear Aβ peptides and prevent their
236:
Mild cognitive impairment (MCI) precedes the overt diagnosis of AD. To be diagnosed with MCI a patient must show memory impairment, a progressive decline in cognitive abilities without presenting symptoms of Parkinson's disease, cerebrovascular diseases, and behavioral or language disorders. Studies
244:
PiB-PET scan of an AD patient (left) compared to an age-matched control (right). Pittsburgh Compound B (PIB) is easily taken up into the brains of AD patients and is used to detect Amyloid beta. Brain regions that are colored red and yellow correspond to a high concentration of PiB, suggesting high
655:
Studies from 2017 showed that the difference in income is present across many income brackets, with only 38.6% of Latinos reporting a household income between $ 50,000 and $ 149,999, in comparison to 45.6% of Non-Hispanic whites. A similar trend was seen with levels of higher education and medical
600:
blood pressure. A patient is diagnosed as hypertensive when their systolic blood pressure is greater than 140 mmHg or diastolic blood pressure is greater than 90 mmHg. Not many people with hypertension are aware that they have the condition. In 2010, 31.1% of adults worldwide had hypertension, but
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Genome-wide association studies (GWAS) in the Hispanic/Latino population indicate that polymorphisms in the BIN1, ABAC7 and CD2AP genes are more significant in Caribbean Hispanics. For instance, one BIN1 mutation that has been explored in this Caribbean Hispanics is rs13426725. Other variants that
227:
Along with the plaques and inflammation, patients with AD also suffer from neurodegeneration, characterized by loss of neurons and synapses (the communication tool for neurons). As a result, the entire brain shrinks in volume (termed brain atrophy), the ventricles grow larger, and the hippocampus
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Many of the comorbidities for AD can be reduced through lifestyle changes. Hypertension can be treated by reducing sodium intake, increasing potassium intake, reducing alcohol consumption, and engaging in at least 150 min of moderate-intensity or 75 min of vigorous-intensity physical activity per
494:
of ApoE receptors and the vacuolar protein sorting 10 (VPS10) domain receptor family. In humans, the SORL1 gene is located on chromosome 11, specifically q232-q24.2. As a protein SORL1 is highly expressed in the brain. SORL1 is an intracellular protein that is expressed in early endosomes and the
416:
While extensive research has been done on the APOE4 gene, more information is available for caucasians than for other ethnic and racial groups. The research focusing on the Hispanic and Latino population, suggests that race is a key variable in assessing the risk of carrying the APOE ε4 allele in
651:
of the Hispanic/Latino population is thought to contribute to their low participation in clinical trials. In the U.S., the income and socioeconomic status of Hispanics and Latinos are lower when compared to White Non-Hispanics. In 2015, a study reported that 25% of the Hispanic/Latino population
569:
can increase one's risk of developing AD as well as increase the rate at which it progresses. In the United States, 33% of the total population suffers from a metabolic disorder (i.e. diabetes and hypertension). Hispanic and Latino adults are at an increased risk of developing these conditions
359:
has been shown to have a neuroprotective effect with carriers of the allele showing a lower prevalence of AD. The neuropathological effects of APOE ε4 are pleiotropic; APOE ε4 impairs uptake of cholesterol by neurons, promotes microglial dysfunction, promotes beta-amyloid aggregation and is
261:
727:
Putative language barriers can also interfere with healthcare for the Hispanic and Latino community. Clinical trials can require participants to be fluent in English, which can potentially exclude older Hispanic and Latino subjects, who might not be fluent in English. Only 40% of the older
323:(APOE) is a lipoprotein, composed of 299 amino acids, that is expressed throughout the body but particularly important in the brain where it is involved in cholesterol metabolism, specifically in the intracellular and extracellular transport, delivery, and distribution. APOE associates with
498:
Analysis of SORL1 polymorphisms in the Hispanic/Latino population using GWAS and whole-genome sequencing (WGS) have shown that several SORL1 mutations are seen in Caribbean Hispanics. Two rare polymorphisms in SORL1 associated with AD were observed in this population, rs117260922-E270K and
177:
Comparing the formation of the plaques, as a result of neuroinflammation, between wild-type (PP) mice, AD-transgenic mice (3xTgAD), and AD patients. The inflammation-induced accumulation of APP fragments (red) represents the seeding point for the aggregation of Amyloid-beta peptides
107:
was signed into law. The goal of this act was for The National Institute of Aging to accelerate research and clinical care of patients with AD; this act also has the benefit of seeking to improve the inclusion of underrepresented populations in AD research and clinical trials.
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González, Hector M.; Tarraf, Wassim; Fornage, Myriam; González, Kevin A.; Chai, Albert; Youngblood, Marston; Abreu, Maria de los Angeles; Zeng, Donglin; Thomas, Sonia; Talavera, Gregory A.; Gallo, Linda C.; Kaplan, Robert; Daviglus, Martha L.; Schneiderman, Neil (2019-12-01).
429:
The human gamma-secretase protein complex imaged using cryo-electron microscopy. The structure contains nicastrin (red), presenilin-1 (orange), PEN-2 (blue), and APH-1 (green). This is a transmembrane protein complex that processes amyloid precursor protein (APP) to Aβ
228:
and cortex shrink in size. As all these pathologies progress, patients begin to experience a decline in memory, cognitive abilities, and independence. The accumulation of neurofibrillary tangles and loss of synaptic fields correlate most closely with cognitive loss.
360:
increases cerebral angiopathy (CAA). The increased incidence of AD associated with the APOE ε4 allele has been proposed to be directly linked to Aβ because it modulates Aβ aggregation and clearance, although increasing evidence points to a multitude of actions.
519:
Adenosine triphosphate (ATP)-binding cassette transporters are a large family of ABC transporters that regulates the efflux of cholesterol in neuronal cells. Two members of the ATP binding cassette transporter family have been implicated in LOAD:
281:, both of which can be found in brain tissue and cerebrospinal fluid (CSF). Aβ provides a biomarker of neuritic plaques, which form when APP cleavage results in an increase in the Aβ42/Aβ40 ratio. Hyperphosphorylated tau serves as a biomarker of
2791:
Vardarajan, Badri N.; Zhang, Yalun; Lee, Joseph H.; Cheng, Rong; Bohm, Christopher; Ghani, Mahdi; Reitz, Christiane; Reyes-Dumeyer, Dolly; Shen, Yufeng; Rogaeva, Ekaterina; St George-Hyslop, Peter; Mayeux, Richard (7 November 2014).
78:
is the most common form of dementia, accounting for 60% of all cases, and is the sixth leading cause of death in the elderly. The disease typically presents itself with intracellular aggregation of hyper-phosphorylated tau, forming
214:
is another pathological component of AD pathology, and is associated with an increase in levels of inflammatory markers. Researchers have also identified many genes linked to immune function that are risk factors for AD, such as
1036:"A research framework for cognitive aging and Alzheimer's disease among diverse US Latinos: Design and implementation of the Hispanic Community Health Study/Study of Latinos—Investigation of Neurocognitive Aging (SOL-INCA)"
660:
25,213 per person, compared to the estimated $ 7750 for senior patients without AD. Increasing efforts are being made to include minorities in clinical research, for instance by providing travel support for participants.
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Briceño, Emily M.; Mehdipanah, Roshanak; Gonzales, Xavier Fonz; Langa, Kenneth M.; Levine, Deborah A.; Garcia, Nelda M.; Longoria, Ruth; Giordani, Bruno J.; Heeringa, Steven G.; Morgenstern, Lewis B. (13 April 2020).
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Oparil, Suzanne; Acelajado, Maria Czarina; Bakris, George L.; Berlowitz, Dan R.; CĂfková, Renata; Dominiczak, Anna F.; Grassi, Guido; Jordan, Jens; Poulter, Neil R.; Rodgers, Anthony; Whelton, Paul K. (2018-03-22).
285:, with the presence of NFTs indicating a disruption in microtubule stability and neuronal injury. Researchers have begun investigating other markers in the CSF, such as markers of neuronal injury, like
203:, dissociates from microtubules and then aggregates with other p-tau monomers forming tau oligomers, fibrils and eventually NFTs. These types of pathologies do not differ across ethnic groups.
273:
Establishing biomarkers for the early detection of AD is an ongoing are of research because pathological changes occur years before symptoms become apparent. Common biomarkers for AD include
857:"Facilitators, Challenges, and Messaging Strategies for Hispanic/Latino Populations Participating in Alzheimer's Disease and Related Dementias Clinical Research: A Literature Review"
757:
Marquez, David X.; Perez, Adriana; Johnson, Julene K.; Jaldin, Michelle; Pinto, Juan; Keiser, Sahru; Tran, Thi; Martinez, Paula; Guerrero, Javier; Portacolone, Elena (26 July 2022).
855:
Massett, Holly A.; Mitchell, Alexandra K.; Alley, Leah; Simoneau, Elizabeth; Burke, Panne; Han, Sae H.; Gallop-Goodman, Gerda; McGowan, Melissa (2021-06-29). Gleason, Carey (ed.).
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2020:
Scheltens, Philip; De Strooper, Bart; Kivipelto, Miia; Holstege, Henne; Chételat, Gael; Teunissen, Charlotte E.; Cummings, Jeffrey; van der Flier, Wiesje M. (2021-04-24).
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second pathway is the non-amyloidogenic pathway and does not produce Aβ. In the amyloidogenic pathway, APP (the parent protein) is trafficked to endosomes, cleaved by
347:
is the most common risk factor for LOAD, increasing genetic risk up to 33-fold, depending on the population (see the table below). Over 50% of LOAD patients have the
23:
are disproportionately affected by Alzheimer's Disease and underrepresented in clinical research. AD is a neurodegenerative disease, characterized by the presence of
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Galicia-Garcia, Unai; Benito-Vicente, Asier; Jebari, Shifa; Larrea-Sebal, Asier; Siddiqi, Haziq; Uribe, Kepa B.; Ostolaza, Helena; MartĂn, CĂ©sar (30 August 2020).
3007:"Association between clusterin gene polymorphism rs11136000 and late‑onset Alzheimer's disease susceptibility: A review and meta‑analysis of case‑control studies"
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3460:"From Sea to Shining Sea and the Great Plains to Patagonia: A Review on Current Knowledge of Diabetes Mellitus in Hispanics/Latinos in the US and Latin America"
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week. Similarly, diabetes can also be treated by increasing physical activity and changing diet. The same lifestyle changes are recommended for AD patients.
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144:(PSEN-2). Onset of sporadic AD has both genetic and environmental risk factors. Some genes of interest in LOAD are the APOE gene, specifically the
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Sortilin-related receptor 1 (SORL1) is a 250-kDa membrane protein with seven distinct domains that make it a member of two receptor families: the
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are most abundantly produced. APP can also be cleaved by alpha and gamma-secretase and undergo non-amyloidogenic processing. NFTs form when the
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Briceño, E; Mehdipanah, R; Gonzales, X; Langa, K; Levine, D; Garcia, N; Longoria, R; Giordani, B; Heeringa, S; Morgenstern, L (2019-08-30).
737:
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Avilés-Santa, M. Larissa; Colón-Ramos, Uriyoán; Lindberg, Nangel M.; Mattei, Josiemer; Pasquel, Francisco J.; Pérez, Cynthia M. (2017).
117:
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Vega, Irving E.; Cabrera, Laura Y.; Wygant, Cassandra M.; Velez-Ortiz, Daniel; Counts, Scott E. (2017-06-23). Abisambra, Jose (ed.).
327:(HDL). The gene for APOE is located on chromosome 19 and exhibits polymorphisms in the population defined by three alleles of APOE:
2219:"The Triggering Receptor Expressed on Myeloid Cells 2: "TREM-ming" the Inflammatory Component Associated with Alzheimer's Disease"
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These alleles differ by only two single nucleotide polymorphisms in exon 4, rs429358 and rs7412 (amino-acid position 112 and 158)
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32:
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3659:. Addressing Unmet Needs in Alzheimer Disease: Implications of Delayed Diagnosis and Examining New and Emerging Therapies.
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Baldacci, Filippo; Lista, Simone; Palermo, Giovanni; Giorgi, Filippo Sean; Vergallo, Andrea; Hampel, Harald (2019-07-03).
20:
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Tejada-Vera B. (2013). Mortality from Alzheimer's Disease in the United States: Data for 2000 and 2010. Hyattsville, MD:
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is a condition characterized by persistently high blood pressure. Two measurements are taken to quantify blood pressure:
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These polymorphisms are not specific to Hispanics/Latinos as they are also observed in non-Hispanic white individuals.
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Genetic risk factors being considered for integration with biomarkers includes ApoE, PSEN1, Bin1, CLU, and SORL1.
3707:
1547:"Enrollment of Racial Minorities in Clinical Trials: Old Problem Assumes New Urgency in the Age of Immunotherapy"
129:
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Nguyen, Thuy Trang; Ta, Qui Thanh Hoai; Nguyen, Thi Kim Oanh; Nguyen, Thi Thuy Dung; Van Giau, Vo (2020-04-30).
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3519:"Diabetes Mellitus in the Hispanic/Latino Population: An Increasing Health Care Challenge in the United States"
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759:"Increasing engagement of Hispanics/Latinos in clinical trials on Alzheimer's disease and related dementias"
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thus releasing the Aβ peptide. This form of APP processing produces multiple Aβ peptides, of which Aβ40 and
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1498:"Alzheimer's Disease in the Latino Community: Intersection of Genetics and Social Determinants of Health"
1320:"Genomics of Alzheimer's disease: Value of high-throughput genomic technologies to dissect its etiology"
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Foster, Evangeline M.; Dangla-Valls, AdriĂ ; Lovestone, Simon; Ribe, Elena M.; Buckley, Noel J. (2019).
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Li, Lanlan; Yu, Xianfeng; Sheng, Can; Jiang, Xueyan; Zhang, Qi; Han, Ying; Jiang, Jiehui (2022-09-15).
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2708:"A Review of the Familial Alzheimer's Disease Locus PRESENILIN 2 and Its Relationship to PRESENILIN 1"
2278:"A review of brain imaging biomarker genomics in Alzheimer's disease: implementation and perspectives"
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1689:"Racial and Ethnic Disparities in Research Studies: The Challenge of Creating More Diverse Cohorts"
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lives in poverty and their median family income was $ 17,800 lower than their white counterparts.
449:. This protein cleaves amyloid precursor protein (APP), after beta-secretase cleavage, to produce
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977:"The neuroinflammatory biomarker YKL-40 for neurodegenerative diseases: advances in development"
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Hispanics and Latinos make up 18% of the U.S. population, however, they are underrepresented in
2458:"Neuropsychological assessment of mild cognitive impairment in Latinx adults: A scoping review"
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Yin, Rui-Hua; Yu, Jin-Tai; Tan, Lan (2015-06-01). "The Role of SORL1 in Alzheimer's Disease".
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2164:"Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?"
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2948:"Clusterin in Alzheimer's Disease: Mechanisms, Genetics, and Lessons From Other Pathologies"
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786:
770:
320:
184:
36:
3517:
Umpierrez, Guillermo E; Gonzalez, Amparo; Umpierrez, Denise; Pimentel, Diana (2007-10-01).
581:
3678:
National Institute of Aging Summary of its Studies of AD in the Hispanic/Latino Population
609:
446:
188:
24:
486:
The X-ray crystallography structure of human SORL1 in complex with A-beta derived peptide
343:
is the more common of the three and is present in 50-90% of the general population. APOE
19:(AD) in the Hispanic/Latino population is becoming a topic of interest in AD research as
922:
116:
There exist two types of Alzheimer's disease: familial Alzheimer's disease, also called
3600:
3565:
3494:
3459:
3424:
3391:
3364:
3329:
3300:
3238:
3205:
3168:
3135:
3105:
3070:
3039:
3006:
2982:
2947:
2914:
2879:
2818:
2793:
2683:
2658:
2490:
2457:
2397:"Validity of Cognitive Assessment Tools for Older Adult Hispanics: A Systematic Review"
2372:
2339:
2312:
2277:
2253:
2218:
2054:
2021:
1945:
1910:
1855:
1820:
1721:
1688:
1651:
1618:
1522:
1497:
1408:
1375:
1270:
1235:
1150:
1117:
1068:
1035:
791:
758:
56:
2037:
906:
3686:
3283:
2438:
2203:
2163:
1617:
Bekris, Lynn M.; Yu, Chang-En; Bird, Thomas D.; Tsuang, Debby W. (24 February 2011).
1586:
1016:
888:
132:(nmEOAD, sporadic) patterns. The three main genes that implicated in familial AD are
2747:
2640:
1821:"Alzheimer's Disease: From Genetic Variants to the Distinct Pathological Mechanisms"
1546:
954:
3267:
589:
558:
491:
454:
450:
274:
192:
88:
84:
1545:
Nazha, Bassel; Mishra, Manoj; Pentz, Rebecca; Owonikoko, Taofeek K. (2019-05-01).
992:
3534:
2127:
1133:
3390:
Olokoba, Abdulfatai B.; Obateru, Olusegun A.; Olokoba, Lateefat B. (July 2012).
294:
290:
278:
240:
196:
2706:
Jiang, Haowei; Jayadev, Suman; Lardelli, Michael; Newman, Morgan (2018-01-01).
2534:
2517:
2294:
2179:
1911:"Alzheimer's Disease: Biomarkers in the Genome, Blood, and Cerebrospinal Fluid"
1051:
763:
Alzheimer's & Dementia: Translational Research & Clinical Interventions
3221:
3087:
2616:
2340:"The diagnosis and management of mild cognitive impairment: a clinical review"
1391:
1336:
1319:
1252:
71:
A healthy brain (left) and the brain of a late-stage Alzheimer's brain (right)
3591:
3542:
3485:
3476:
3415:
3355:
3291:
3229:
3159:
3096:
3030:
2973:
2964:
2905:
2731:
2674:
2624:
2543:
2481:
2422:
2363:
2303:
2244:
2187:
2135:
2045:
1936:
1927:
1846:
1837:
1778:
1712:
1642:
1634:
1570:
1399:
1345:
1261:
1141:
1059:
1000:
938:
782:
2355:
930:
355:
allele increases the risk of developing Alzheimer's by a factor of 4. APOE
157:
52:
3625:"About One-in-Four U.S. Hispanics Have Heard of Latinx, but Just 3% Use It"
3609:
3550:
3503:
3433:
3373:
3309:
3247:
3177:
3114:
3048:
3005:
Du, Wenjin; Tan, Jiping; Xu, Wei; Chen, Jinwen; Wang, Luning (2016-11-01).
2991:
2923:
2827:
2739:
2692:
2632:
2499:
2430:
2395:
Arévalo, Sandra P.; Kress, Jennifer; Rodriguez, Francisca S. (April 2020).
2381:
2321:
2262:
2195:
2143:
2063:
1954:
1864:
1786:
1730:
1660:
1578:
1531:
1417:
1374:
Liu, Chia-Chen; Kanekiyo, Takahisa; Xu, Huaxi; Bu, Guojun (February 2013).
1353:
1279:
1159:
1077:
1008:
946:
880:
800:
3022:
2235:
3582:
3346:
3151:
2896:
2794:"Coding mutations in SORL 1 and Alzheimer disease: SORL1 Variants and AD"
1704:
550:
298:
3407:
3268:"Epidemiology and Management of Hypertension in the Hispanic Population"
1562:
511:
2723:
2473:
2112:"Bridging integrator 1 (BIN1): form, function, and Alzheimer's disease"
1513:
1376:"Apolipoprotein E and Alzheimer disease: risk, mechanisms, and therapy"
872:
774:
562:
458:
187:(BACE), after which it moves back to the cell surface to be cleaved by
3653:"Economic Burden of Alzheimer Disease and Managed Care Considerations"
2809:
2657:
KHANAHMADI, Mohammad; FARHUD, Dariush D.; MALMIR, Maryam (July 2015).
2413:
2396:
1116:
Reitz, Christiane; Rogaeva, Ekaterina; Beecham, Gary W. (2020-10-06).
445:(PSEN1) is the catalytic subunit of the transmembrane protein complex
2841:
Stieger, Bruno (2007-01-01), Enna, S. J.; Bylund, David B. (eds.),
1819:
Sun, Qiying; Xie, Nina; Tang, Beisha; Li, Rena; Shen, Yong (2017).
1236:"Comprehensive Review on Alzheimer's Disease: Causes and Treatment"
3566:"Type 3 Diabetes and Its Role Implications in Alzheimer's Disease"
525:
521:
510:
499:
rs143571823-T947M, as well as a common variant (rs2298813-A528T)
442:
424:
259:
216:
153:
145:
141:
137:
48:
40:
1769:
1752:
3204:
Mills, Katherine T; Stefanescu, Andrei; He, Jiang (April 2020).
2555:
2553:
2518:"Culture and Diagnosis of MCI in Hispanics: A Literature Review"
1751:
Piaceri, Irene; Nacmias, Benedetta; Sorbi, Sandro (2013-01-01).
532:
increases AD risk in African Americans and Caribbean Hispanics.
149:
44:
425:
1972:
1970:
1968:
1966:
1964:
634:
The distribution of Hispanics and Latinos in the United States
2878:
Dib, Shiraz; Pahnke, Jens; Gosselet, Fabien (27 April 2021).
3071:"The Impact of Disease Comorbidities in Alzheimer's Disease"
2659:"Genetic of Alzheimer's Disease: A Narrative Review Article"
2880:"Role of ABCA7 in Human Health and in Alzheimer's Disease"
1118:"Late-onset vs nonmendelian early-onset Alzheimer disease"
905:
Goedert, Michel; Spillantini, Maria Grazia (2006-11-03).
1753:"Genetics of familial and sporadic Alzheimer's disease"
3392:"Type 2 Diabetes Mellitus: A Review of Current Trends"
3323:
3321:
3319:
3069:
Santiago, Jose A.; Potashkin, Judith A. (2021-02-12).
1551:
American Society of Clinical Oncology Educational Book
120:(EOAD), and sporadic Alzheimer's disease, also called
549:
Studies have shown that metabolic disorders, such as
364:
The risk of developing AD with two copies of the APOE
3646:
3644:
3453:
3451:
3449:
3447:
3445:
3443:
2338:
Langa, Kenneth M.; Levine, Deborah A. (2014-12-17).
2110:
Tan, Meng-Shan; Yu, Jin-Tai; Tan, Lan (2013-10-01).
264:
The role of genetic mutations in Alzheimer's Disease
1978:"What Happens to the Brain in Alzheimer's Disease?"
2786:
2784:
2782:
2780:
2778:
2652:
2650:
2015:
2013:
2011:
2009:
2007:
2005:
2003:
2001:
1999:
1997:
1318:Tosto, Giuseppe; Reitz, Christiane (2016-12-01).
199:, which is involved in microtubule stability, is
3064:
3062:
3060:
3058:
2847:xPharm: The Comprehensive Pharmacology Reference
1229:
1227:
1225:
1223:
1221:
1219:
1217:
1215:
1213:
1211:
1209:
1207:
1205:
1203:
1201:
1199:
1197:
1195:
1193:
1191:
1189:
169:Amyloid beta plaques and neurofibrillary tangles
3385:
3383:
2511:
2509:
2450:
2448:
1746:
1744:
1742:
1740:
1234:Breijyeh, Zeinab; Karaman, Rafik (2020-12-08).
1187:
1185:
1183:
1181:
1179:
1177:
1175:
1173:
1171:
1169:
1028:
1026:
970:
968:
966:
964:
850:
848:
846:
844:
842:
840:
838:
836:
834:
832:
830:
3261:
3259:
3257:
3128:
3126:
3124:
2941:
2939:
2937:
2935:
2933:
1904:
1902:
1900:
1898:
1896:
1894:
1682:
1680:
1678:
1676:
1674:
1672:
1670:
1612:
1610:
1608:
1606:
1604:
1602:
1600:
1598:
1596:
900:
898:
828:
826:
824:
822:
820:
818:
816:
814:
812:
810:
492:low-density lipoprotein receptor (LDLR) family
438:The processing of APP by α, β and γ-secretases
366:𝜀4 allele across various racial-ethnic groups
3629:Pew Research Center's Hispanic Trends Project
3330:"Pathophysiology of Type 2 Diabetes Mellitus"
3199:
3197:
3195:
3193:
3191:
3189:
3187:
2333:
2331:
1892:
1890:
1888:
1886:
1884:
1882:
1880:
1878:
1876:
1874:
1623:Journal of Geriatric Psychiatry and Neurology
1491:
1489:
1487:
1485:
1483:
1481:
1479:
1477:
1475:
1473:
1471:
1469:
1467:
1465:
1463:
1461:
1459:
1457:
1455:
1453:
1451:
1449:
1447:
1313:
1311:
1309:
1111:
1109:
1107:
8:
3523:The American Journal of the Medical Sciences
2762:U.S. Department of Health and Human Services
2157:
2155:
2153:
2105:
2103:
2101:
2099:
2097:
2095:
2093:
1445:
1443:
1441:
1439:
1437:
1435:
1433:
1431:
1429:
1427:
1307:
1305:
1303:
1301:
1299:
1297:
1295:
1293:
1291:
1289:
1105:
1103:
1101:
1099:
1097:
1095:
1093:
1091:
1089:
1087:
351:allele and that having even one copy of the
316:A 22K fragment of the APOE4 protein (IB68).
3570:International Journal of Molecular Sciences
3334:International Journal of Molecular Sciences
2884:International Journal of Molecular Sciences
2873:
2871:
2598:
2596:
2594:
2592:
2590:
2588:
2586:
2584:
2582:
2580:
2091:
2089:
2087:
2085:
2083:
2081:
2079:
2077:
2075:
2073:
1814:
1812:
1810:
1808:
1806:
1804:
1802:
1800:
1798:
1796:
474:increase the risk of AD include rs6733839.
2766:Centers for Disease Control and Prevention
2401:Journal of the American Geriatrics Society
1369:
1367:
1365:
1363:
662:
626:Hispanics and Latinos in clinical research
3599:
3581:
3493:
3475:
3423:
3363:
3345:
3299:
3237:
3206:"The global epidemiology of hypertension"
3167:
3104:
3086:
3038:
2981:
2963:
2913:
2895:
2817:
2682:
2533:
2489:
2412:
2371:
2311:
2293:
2252:
2234:
2223:Oxidative Medicine and Cellular Longevity
2162:Leng, Fangda; Edison, Paul (March 2021).
2053:
1944:
1926:
1854:
1836:
1768:
1720:
1650:
1521:
1407:
1335:
1269:
1251:
1149:
1067:
790:
3272:American Journal of Cardiovascular Drugs
1909:Huynh, Rose Ann; Mohan, Chandra (2017).
629:
580:
481:
433:
362:
311:
239:
172:
105:National Alzheimer's Disease Project Act
66:
2843:"ABC1, ATP Binding Cassette Permease 1"
2561:"How Biomarkers Help Diagnose Dementia"
1326:. Genetics of multifactorial diseases.
749:
83:, and the extracellular aggregation of
3657:Supplements and Featured Publications
3011:Experimental and Therapeutic Medicine
2770:National Center for Health Statistics
7:
3713:Hispanic and Latino American society
3693:Race and health in the United States
2849:, New York: Elsevier, pp. 1–3,
2522:Archives of Clinical Neuropsychology
738:Race and health in the United States
515:The Cryo-EM structure of Human ABCA1
3651:Winston Wong, PharmD (2020-08-17).
1825:Frontiers in Molecular Neuroscience
1687:Konkel, Lindsey (1 December 2015).
585:The clinical stages of hypertension
907:"A Century of Alzheimer's Disease"
14:
3623:Greenwood, Shannon (2020-08-11).
3266:Guzman, Nicolas J. (2012-06-01).
1693:Environmental Health Perspectives
507:ATP binding cassette transporters
3284:10.2165/11631520-000000000-00000
2663:Iranian Journal of Public Health
526:ABC Subfamily A member 7 (ABCA7)
522:ABC Subfamily A Member 1 (ABCA1)
287:Visinin-Like-Protein-1 (VILIP-1)
3140:Nature Reviews. Disease Primers
3075:Frontiers in Aging Neuroscience
2282:Translational Neurodegeneration
1619:"Genetics of Alzheimer Disease"
118:early-onset Alzheimer's disease
2712:Journal of Alzheimer's Disease
1502:Journal of Alzheimer's Disease
861:Journal of Alzheimer's Disease
283:neurofibrillary tangles (NFTs)
122:late-onset Alzheimer's disease
81:neurofibrillary tangles (NFTs)
1:
2038:10.1016/S0140-6736(20)32205-4
1324:Molecular and Cellular Probes
993:10.1080/14789450.2019.1628643
3698:Alzheimer's disease research
3535:10.1097/MAJ.0b013e3180a6efe3
2217:Rohn, Troy T. (2013-03-06).
2128:10.1016/j.molmed.2013.06.004
2116:Trends in Molecular Medicine
1134:10.1212/NXG.0000000000000512
664:The Cost of AD Care in 2020
255:Positron emission tomography
150:bridging Integrator 1 (BIN1)
45:bridging Integrator 1 (BIN1)
2565:National Institute on Aging
1982:National Institute on Aging
981:Expert Review of Proteomics
3729:
3464:Frontiers in Endocrinology
3210:Nature Reviews. Nephrology
2295:10.1186/s40035-022-00315-z
2180:10.1038/s41582-020-00435-y
1052:10.1016/j.jalz.2019.08.192
1040:Alzheimer's & Dementia
245:amounts of amyloid deposit
95:Hispanic/Latino population
3222:10.1038/s41581-019-0244-2
3088:10.3389/fnagi.2021.631770
2952:Frontiers in Neuroscience
2617:10.1007/s12035-014-8742-5
1392:10.1038/nrneurol.2012.263
1380:Nature Reviews. Neurology
1337:10.1016/j.mcp.2016.09.001
1253:10.3390/molecules25245789
325:high-density lipoproteins
232:Mild cognitive impairment
134:amyloid precursor protein
59:and receive proper care.
33:amyloid precursor protein
3477:10.3389/fendo.2017.00298
2965:10.3389/fnins.2019.00164
2535:10.1093/arclin/acz029.06
2168:Nature Reviews Neurology
1928:10.3389/fneur.2017.00102
1838:10.3389/fnmol.2017.00319
1635:10.1177/0891988710383571
277:and hyperphosphorylated
2356:10.1001/jama.2014.13806
1757:Frontiers in Bioscience
931:10.1126/science.1132814
377:𝜀4 Association with AD
62:
29:neurofibrillary tangles
2605:Molecular Neurobiology
1915:Frontiers in Neurology
672:Cost in Billions ($ )
635:
586:
555:cardiovascular disease
516:
487:
439:
431:
317:
265:
246:
179:
164:Pathology and symptoms
72:
3023:10.3892/etm.2016.3734
2022:"Alzheimer's disease"
633:
584:
514:
485:
437:
428:
315:
263:
243:
176:
70:
21:Hispanics and Latinos
3583:10.3390/ijms21093165
3396:Oman Medical Journal
3347:10.3390/ijms21176275
3152:10.1038/nrdp.2018.14
2897:10.3390/ijms22094603
2032:(10284): 1577–1590.
1705:10.1289/ehp.123-A297
649:socioeconomic status
643:Socioeconomic status
207:Chronic inflammation
41:presenilin 1 (PSEN1)
25:amyloid-beta plaques
3408:10.5001/omj.2012.68
2798:Annals of Neurology
2236:10.1155/2013/860959
1563:10.1200/EDBK_100021
1122:Neurology: Genetics
923:2006Sci...314..777G
665:
368:
201:hyperphosphorylated
76:Alzheimer's disease
63:Alzheimer's disease
17:Alzheimer's disease
2724:10.3233/JAD-180656
2474:10.1037/neu0000628
1514:10.3233/JAD-161261
873:10.3233/JAD-201463
775:10.1002/trc2.12331
663:
636:
587:
517:
488:
440:
432:
391:African Americans
363:
318:
266:
247:
180:
73:
2856:978-0-08-055232-3
2810:10.1002/ana.24305
2414:10.1111/jgs.16300
2350:(23): 2551–2561.
1699:(12): A297–A302.
1046:(12): 1624–1632.
917:(5800): 777–781.
720:
719:
414:
413:
223:Neurodegeneration
212:Neuroinflammation
101:clinical research
3720:
3708:Cultural studies
3665:
3664:
3648:
3639:
3638:
3636:
3635:
3620:
3614:
3613:
3603:
3585:
3561:
3555:
3554:
3514:
3508:
3507:
3497:
3479:
3455:
3438:
3437:
3427:
3387:
3378:
3377:
3367:
3349:
3325:
3314:
3313:
3303:
3263:
3252:
3251:
3241:
3201:
3182:
3181:
3171:
3130:
3119:
3118:
3108:
3090:
3066:
3053:
3052:
3042:
3017:(5): 2915–2927.
3002:
2996:
2995:
2985:
2967:
2943:
2928:
2927:
2917:
2899:
2875:
2866:
2865:
2864:
2863:
2838:
2832:
2831:
2821:
2788:
2773:
2758:
2752:
2751:
2718:(4): 1323–1339.
2703:
2697:
2696:
2686:
2654:
2645:
2644:
2600:
2575:
2574:
2572:
2571:
2557:
2548:
2547:
2537:
2513:
2504:
2503:
2493:
2452:
2443:
2442:
2416:
2392:
2386:
2385:
2375:
2335:
2326:
2325:
2315:
2297:
2273:
2267:
2266:
2256:
2238:
2214:
2208:
2207:
2159:
2148:
2147:
2107:
2068:
2067:
2057:
2017:
1992:
1991:
1989:
1988:
1974:
1959:
1958:
1948:
1930:
1906:
1869:
1868:
1858:
1840:
1816:
1791:
1790:
1772:
1748:
1735:
1734:
1724:
1684:
1665:
1664:
1654:
1614:
1591:
1590:
1542:
1536:
1535:
1525:
1493:
1422:
1421:
1411:
1371:
1358:
1357:
1339:
1315:
1284:
1283:
1273:
1255:
1231:
1164:
1163:
1153:
1113:
1082:
1081:
1071:
1030:
1021:
1020:
972:
959:
958:
902:
893:
892:
852:
805:
804:
794:
754:
723:Language barrier
666:
610:Type-II diabetes
369:
321:Apolipoprotein E
89:neuritic plaques
37:Apolipoprotein E
3728:
3727:
3723:
3722:
3721:
3719:
3718:
3717:
3683:
3682:
3674:
3669:
3668:
3650:
3649:
3642:
3633:
3631:
3622:
3621:
3617:
3563:
3562:
3558:
3516:
3515:
3511:
3457:
3456:
3441:
3389:
3388:
3381:
3327:
3326:
3317:
3265:
3264:
3255:
3203:
3202:
3185:
3132:
3131:
3122:
3068:
3067:
3056:
3004:
3003:
2999:
2945:
2944:
2931:
2877:
2876:
2869:
2861:
2859:
2857:
2840:
2839:
2835:
2790:
2789:
2776:
2759:
2755:
2705:
2704:
2700:
2656:
2655:
2648:
2602:
2601:
2578:
2569:
2567:
2559:
2558:
2551:
2515:
2514:
2507:
2462:Neuropsychology
2454:
2453:
2446:
2394:
2393:
2389:
2337:
2336:
2329:
2275:
2274:
2270:
2216:
2215:
2211:
2161:
2160:
2151:
2122:(10): 594–603.
2109:
2108:
2071:
2019:
2018:
1995:
1986:
1984:
1976:
1975:
1962:
1908:
1907:
1872:
1818:
1817:
1794:
1750:
1749:
1738:
1686:
1685:
1668:
1616:
1615:
1594:
1544:
1543:
1539:
1495:
1494:
1425:
1373:
1372:
1361:
1317:
1316:
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974:
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669:Payment Source
645:
628:
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579:
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509:
480:
467:
455:amyloid beta-42
447:gamma-secretase
423:
310:
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189:gamma secretase
171:
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114:
97:
65:
57:clinical trials
12:
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5:
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3672:External links
3670:
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3253:
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3183:
3136:"Hypertension"
3120:
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2929:
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2804:(2): 215–227.
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817:
815:
813:
811:
807:
802:
798:
793:
788:
784:
780:
776:
772:
769:(1): e12331.
768:
764:
760:
753:
750:
743:
739:
736:
735:
731:
729:
722:
716:
713:
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583:
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568:
564:
560:
556:
552:
545:Comorbidities
544:
542:
535:
533:
531:
527:
523:
513:
506:
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502:
496:
493:
484:
477:
475:
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464:
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314:
307:
305:
302:
300:
296:
292:
288:
284:
280:
276:
268:
262:
258:
256:
250:Brain imaging
249:
242:
238:
231:
229:
222:
220:
218:
213:
206:
204:
202:
198:
194:
190:
186:
175:
168:
163:
161:
159:
155:
151:
147:
143:
139:
135:
131:
130:non-mendelian
127:
123:
119:
111:
109:
106:
102:
94:
92:
90:
86:
82:
77:
69:
60:
58:
54:
50:
46:
42:
38:
34:
30:
26:
22:
18:
3660:
3656:
3632:. Retrieved
3628:
3618:
3573:
3569:
3559:
3526:
3522:
3512:
3467:
3463:
3399:
3395:
3340:(17): 6275.
3337:
3333:
3275:
3271:
3213:
3209:
3143:
3139:
3078:
3074:
3014:
3010:
3000:
2955:
2951:
2887:
2883:
2860:, retrieved
2846:
2836:
2801:
2797:
2756:
2715:
2711:
2701:
2666:
2662:
2608:
2604:
2568:. Retrieved
2564:
2525:
2521:
2465:
2461:
2404:
2400:
2390:
2347:
2343:
2285:
2281:
2271:
2226:
2222:
2212:
2171:
2167:
2119:
2115:
2029:
2025:
1985:. Retrieved
1981:
1918:
1914:
1828:
1824:
1770:10.2741/E605
1760:
1756:
1696:
1692:
1626:
1622:
1557:(39): 3–10.
1554:
1550:
1540:
1505:
1501:
1383:
1379:
1327:
1323:
1246:(24): 5789.
1243:
1239:
1125:
1121:
1043:
1039:
984:
980:
914:
910:
864:
860:
766:
762:
752:
726:
714:
709:
658:
654:
646:
637:
620:
608:
590:Hypertension
588:
577:Hypertension
571:
559:hypertension
548:
539:
529:
518:
500:
497:
489:
472:
468:
451:Amyloid beta
443:Presenilin 1
441:
415:
376:
365:
356:
352:
348:
344:
340:
336:
332:
328:
319:
303:
275:amyloid beta
272:
253:
235:
226:
210:
193:Aβ42 peptide
181:
146:ApoE4 allele
142:presenilin-2
138:Presenilin-1
128:(mEOAD) and
115:
98:
85:amyloid beta
74:
15:
3703:Gerontology
3576:(9): 3165.
2890:(9): 4603.
2528:(7): 1239.
2229:: e860959.
1128:(5): e512.
372:Population
297:, TGF, and
295:interleukin
291:Neurogranin
197:tau protein
3687:Categories
3634:2022-11-15
3081:: 631770.
2862:2022-12-03
2570:2022-12-05
1987:2022-12-05
744:References
567:depression
478:SORL1 gene
421:PSEN1 gene
383:Caucasian
269:Biomarkers
140:(PSEN-1),
3592:1422-0067
3543:0002-9629
3486:1664-2392
3416:1999-768X
3356:1422-0067
3292:1179-187X
3230:1759-5061
3160:2056-676X
3146:: 18014.
3097:1663-4365
3031:1792-0981
2974:1662-453X
2906:1422-0067
2732:1387-2877
2675:2251-6085
2625:1559-1182
2544:1873-5843
2482:1931-1559
2439:209511214
2423:1532-5415
2364:1538-3598
2304:2047-9158
2288:(1): 42.
2245:1942-0900
2204:229163795
2188:1759-4766
2136:1471-4914
2046:1474-547X
1937:1664-2295
1847:1662-5099
1779:1945-0494
1713:0091-6765
1643:0891-9887
1587:157059400
1571:1548-8748
1400:1759-4758
1346:0890-8508
1262:1420-3049
1240:Molecules
1142:2376-7839
1060:1552-5260
1017:189813489
1001:1478-9450
939:0036-8075
889:234745473
783:2352-8737
685:Medicaid
677:Medicare
617:Lifestyle
598:diastolic
536:Clusterin
465:BIN1 gene
407:Japanese
399:Hispanic
308:APOE gene
299:micro-RNA
158:clusterin
126:mendelian
53:Clusterin
3610:32365816
3551:18030184
3504:29176960
3434:23071876
3374:32872570
3310:22583147
3248:32024986
3178:29565029
3115:33643025
3049:27882096
2992:30872998
2924:33925691
2828:25382023
2748:53247231
2740:30412492
2693:26576367
2641:16362596
2633:24833601
2500:32281811
2431:31886524
2382:25514304
2322:36109823
2263:23533697
2196:33318676
2144:23871436
2064:33667416
1955:28373857
1865:29056900
1787:23276979
1731:26625444
1661:21045163
1579:31099618
1532:28527211
1418:23296339
1354:27618776
1280:33302541
1160:33225065
1078:31759880
1009:31195846
955:13906986
947:17082447
881:33998537
801:35910673
732:See also
605:Diabetes
594:systolic
551:diabetes
430:peptide.
329:𝜀2, 𝜀3
178:(green).
3601:7246646
3495:5687125
3470:: 298.
3425:3464757
3365:7503727
3301:3624012
3239:7998524
3169:6477925
3106:7906983
3040:5103725
2983:6403191
2958:: 164.
2915:8124837
2819:4367199
2684:4645760
2491:8209654
2373:4269302
2313:9476275
2254:3606781
2055:8354300
1946:5357660
1921:: 102.
1856:5635057
1831:: 319.
1722:4670264
1652:3044597
1523:5874398
1409:3726719
1271:7764106
1151:7673282
1069:6925624
919:Bibcode
911:Science
792:9322823
563:obesity
459:Yarumal
160:(CLU).
136:(APP),
39:APOE),
35:(APP),
3608:
3598:
3590:
3549:
3541:
3502:
3492:
3484:
3432:
3422:
3414:
3372:
3362:
3354:
3308:
3298:
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