105:
body pathology selectively travels through the CNS, targeting thin and largely unmyelinated neurons. Braak et al., therefore, developed a staging system that characterizes disease progression. This system is divided into six different stages, with each stage being attributed to abnormal pathology in particular neurological structures. In terms of symptomatology, the type and severity of symptoms is correlated to progression through the Braak stages. Early stages are characterized by non-motor symptoms, such as a lessened sense of smell or constipation. Motor symptoms are often displayed around the mid-stage state, and cognitive symptoms arise as later Braak stages are reached. Braak and colleagues further state that the disease begins in the enteric nervous system and gains entry to the CNS through the vagus nerve.
232:
114:
20:
42:
104:
in 2003. Braak and colleagues state that
Parkinson's disease begins when a foreign agent enters the body via the nose or gastrointestinal system and travels into the central nervous system (CNS). The presence of Lewy bodies in the enteric and peripheral nervous systems supports their claim. This Lewy
214:
The disease has started to invade the neocortex and spreads into the structures of the temporal, parietal, and frontal lobes. Cell death can be observed in the substantia nigra, the dorsal motor nucleus of the vagus nerve, the gigantocellular reticular nucleus, and the locus ceruleus.
381:
Obeso, Jose A.; Rodriguez-Oroz, Maria C.; Goetz, Christopher G.; Marin, Concepcion; Kordower, Jeffrey H.; Rodriguez, Manuel; Hirsch, Etienne C.; Farrer, Matthew; Schapira, Anthony H. V. (June 2010). "Missing pieces in the
Parkinson's disease puzzle".
117:
Braak
Staging: Yellow represents the origin of Parkinson's pathology. Pink/purple represent Stages 1 and 2. Blue represents Stages 3 and 4. Orange represents Stage 5. Yellow represents full neocortex engagement and Stage
166:
At the beginning of Stage 3, the disease has entered the substantia nigra and Lewy body lesions begin to form in the pars compacta. The latter half of this stage involves disease progression into the
84:, with up to 70% of the cells affected by the time the patient dies. The mechanisms by which the brain cells are lost are varied. One mechanism consists of an abnormal accumulation of the protein
64:. These methods are used both in research and for the clinical diagnosis of these diseases and are obtained by performing an autopsy of the brain.
23:
A. Schematic initial progression of Lewy body deposits in the first stages of
Parkinson's Disease, as proposed by Braak and colleagues.
585:
223:
The disease has fully invaded the neocortex, affecting the motor and sensory areas in the brain. The disease is at its most severe.
147:
134:
are affected. Lewy neurites, thread-like alpha-synuclein aggregates, are more prevalent than globular Lewy bodies in this stage.
739:
734:
123:
29:
in initial PD compared with a group of participants without the disease in a neuroimaging study which concluded that
452:
Braak, Heiko; Tredici, Kelly Del; RΓΌb, Udo; Vos, Rob A. I. de; Steur, Ernst N. H. Jansen; Braak, Eva (2003-03-01).
131:
150:
of the medulla oblongata. The disease then moves up the brainstem, traveling from the medullary structures to the
626:
Rietdijk, Carmen D.; Perez-Pardo, Paula; Garssen, Johan; Wezel, Van; A, Richard J.; Kraneveld, Aletta D. (2017).
247:
of a patient who had died with
Alzheimer's disease at Braak stage VI. The bar = 25 microns (0.025 millimeters).
453:
26:
252:
73:
61:
57:
142:
In addition to the pathology observed in Stage 1, Stage 2 is characterized by additional lesions in the
231:
186:
Stage 4 is characterized by severe dopaminergic cell destruction in the pars compacta. There is also
122:
The disease begins in structures of the lower brainstem and the olfactory system. In particular, the
251:
Staging in
Alzheimer's disease was described by Braak in 1991. Braak stages I and II are used when
710:
489:
415:
702:
667:
649:
608:
551:
533:
481:
473:
407:
399:
363:
325:
256:
187:
155:
127:
694:
657:
639:
600:
541:
523:
465:
391:
355:
315:
305:
77:
113:
88:
bound to ubiquitin in the damaged cells. This protein accumulation forms inclusions called
19:
586:"A critical evaluation of current staging of Ξ±-synuclein pathology in Lewy body disorders"
294:"Regional brain stem atrophy in idiopathic Parkinson's disease detected by anatomical MRI"
167:
151:
85:
41:
685:
Braak, H.; Braak, E. (1991). "Neuropathological stageing of
Alzheimer-related changes".
662:
627:
546:
511:
320:
293:
34:
469:
728:
272:
171:
81:
510:
Visanji, Naomi P.; Brooks, Patricia L.; Hazrati, Lili-Naz; Lang, Anthony E. (2013).
493:
178:. Further, structures affected in Stages 1 and 2 begin to develop more Lewy bodies.
419:
143:
714:
604:
310:
264:
236:
101:
191:
30:
653:
644:
537:
477:
403:
268:
244:
195:
175:
89:
46:
671:
612:
555:
485:
411:
367:
329:
706:
528:
359:
259:
region of the brain, stages III and IV when there is also involvement of
203:
199:
698:
206:. There is significant damage done to the anterior olfactory nucleus.
260:
240:
454:"Staging of brain pathology related to sporadic Parkinson's disease"
395:
198:
remains unaffected. In particular, pathology can be observed in the
512:"The prion hypothesis in Parkinson's disease: Braak to the future"
230:
112:
56:
refers to two methods used to classify the degree of pathology in
40:
593:
Biochimica et
Biophysica Acta (BBA) - Molecular Basis of Disease
243:
cell bodies (arrow) and neuronal extensions (arrowhead) in the
80:. In particular, this death occurs in the ventral part of the
271:
involvement. This should not be confused with the degree of
158:. Similar to Stage 1, Lewy neurites outnumber Lewy bodies.
292:
Jubault T, Brambati SM, Degroot C, et al. (2009).
628:"Exploring Braak's Hypothesis of Parkinson's Disease"
346:
Davie, CA (2008). "A review of
Parkinson's disease".
100:
The staging in
Parkinson's disease was described by
33:damage may be the first identifiable stage of PD
25:B. Localization of the area of significant brain
239:, which constitutes neurofibrillary tangles, in
505:
503:
8:
275:involvement, which progresses differently.
661:
643:
545:
527:
319:
309:
72:The main pathological characteristic of
18:
284:
267:, and V and VI when there is extensive
124:dorsal motor nucleus of the vagus nerve
45:Positive Alpha-Synuclein staining of a
255:involvement is confined mainly to the
49:in a patient with Parkinson's disease.
7:
579:
577:
575:
573:
571:
569:
567:
565:
516:Acta Neuropathologica Communications
447:
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435:
433:
431:
429:
341:
339:
16:Classification of disease severity
14:
584:Jellinger, Kurt A. (2009-07-01).
148:gigantocellular reticular nucleus
1:
470:10.1016/s0197-4580(02)00065-9
605:10.1016/j.bbadis.2008.07.006
311:10.1371/journal.pone.0008247
202:and in the subnuclei of the
174:-rich neurons in the basal
756:
132:anterior olfactory nucleus
235:Abnormal accumulation of
645:10.3389/fneur.2017.00037
168:basal nucleus of Meynert
595:. Parkinson's Disease.
226:
67:
632:Frontiers in Neurology
253:neurofibrillary tangle
248:
119:
95:
50:
38:
687:Acta Neuropathologica
529:10.1186/2051-5960-1-2
458:Neurobiology of Aging
234:
116:
76:is cell death in the
44:
22:
263:regions such as the
740:Alzheimer's disease
735:Parkinson's disease
227:Alzheimer's disease
74:Parkinson's disease
68:Parkinson's disease
62:Alzheimer's disease
58:Parkinson's disease
699:10.1007/BF00308809
360:10.1093/bmb/ldn013
249:
120:
51:
39:
194:involvement; the
156:pontine tegmentum
128:medulla oblongata
747:
719:
718:
682:
676:
675:
665:
647:
623:
617:
616:
590:
581:
560:
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549:
531:
507:
498:
497:
449:
424:
423:
378:
372:
371:
343:
334:
333:
323:
313:
289:
78:substantia nigra
27:volume reduction
755:
754:
750:
749:
748:
746:
745:
744:
725:
724:
723:
722:
684:
683:
679:
625:
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620:
588:
583:
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563:
509:
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451:
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427:
396:10.1038/nm.2165
384:Nature Medicine
380:
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375:
345:
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337:
291:
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257:transentorhinal
229:
221:
212:
184:
170:, a cluster of
164:
140:
111:
98:
86:alpha-synuclein
70:
24:
17:
12:
11:
5:
753:
751:
743:
742:
737:
727:
726:
721:
720:
677:
618:
599:(7): 730β740.
561:
499:
464:(2): 197β211.
425:
390:(6): 653β661.
373:
335:
283:
282:
280:
277:
228:
225:
220:
217:
211:
208:
183:
180:
163:
160:
152:locus ceruleus
139:
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110:
107:
97:
96:Braak's theory
94:
69:
66:
35:neuropathology
15:
13:
10:
9:
6:
4:
3:
2:
752:
741:
738:
736:
733:
732:
730:
716:
712:
708:
704:
700:
696:
693:(4): 239β59.
692:
688:
681:
678:
673:
669:
664:
659:
655:
651:
646:
641:
637:
633:
629:
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619:
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349:
348:Br. Med. Bull
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322:
317:
312:
307:
304:(12): e8247.
303:
299:
295:
288:
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278:
276:
274:
273:senile plaque
270:
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224:
218:
216:
209:
207:
205:
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173:
172:acetylcholine
169:
161:
159:
157:
153:
149:
145:
137:
135:
133:
129:
125:
115:
108:
106:
103:
93:
91:
87:
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82:pars compacta
79:
75:
65:
63:
59:
55:
54:Braak staging
48:
43:
36:
32:
28:
21:
690:
686:
680:
635:
631:
621:
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592:
519:
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461:
457:
387:
383:
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351:
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301:
297:
287:
250:
222:
213:
185:
165:
144:raphe nuclei
141:
121:
99:
71:
53:
52:
269:neocortical
265:hippocampus
237:tau protein
102:Heiko Braak
90:Lewy bodies
729:Categories
354:: 109β27.
279:References
192:allocortex
188:mesocortex
31:brain stem
654:1664-2295
538:2051-5960
478:0197-4580
404:1078-8956
245:neocortex
196:neocortex
176:forebrain
47:Lewy body
672:28243222
613:18718530
556:24252164
494:22798538
486:12498954
412:20495568
368:18398010
330:20011063
298:PLOS ONE
241:neuronal
204:thalamus
200:amygdala
707:1759558
663:5304413
547:3776210
420:3146438
321:2784293
219:Stage 6
210:Stage 5
182:Stage 4
162:Stage 3
154:in the
138:Stage 2
126:in the
109:Stage 1
715:668690
713:
705:
670:
660:
652:
638:: 37.
611:
554:
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418:
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366:
328:
318:
261:limbic
711:S2CID
589:(PDF)
522:: 2.
490:S2CID
416:S2CID
703:PMID
668:PMID
650:ISSN
609:PMID
597:1792
552:PMID
534:ISSN
482:PMID
474:ISSN
408:PMID
400:ISSN
364:PMID
326:PMID
190:and
146:and
130:and
60:and
695:doi
658:PMC
640:doi
601:doi
542:PMC
524:doi
466:doi
392:doi
356:doi
316:PMC
306:doi
731::
709:.
701:.
691:82
689:.
666:.
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634:.
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607:.
591:.
564:^
550:.
540:.
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428:^
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352:86
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338:^
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296:.
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717:.
697::
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636:8
615:.
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308::
302:4
37:.
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