{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T11:14:29Z","timestamp":1778843669917,"version":"3.51.4"},"reference-count":14,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:00:00Z","timestamp":1628812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disord Clin Pract"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>\u03b1\u2010synuclein aggregates in the form of Lewy bodies and Lewy neurites are the pathological hallmark of Parkinson disease (PD) and dementia with Lewy bodies (DLB). Autopsy studies suggest that \u03b1\u2010synuclein aggregates appear in localized areas of the central nervous system before spreading in a sequential pattern from the brainstem to the cerebral cortex, known as the Braak hypothesis. Increased prevalence of peripheral neuropathy in PD is recognized, with multiple hypothesized mechanisms including \u03b1\u2010synuclein deposition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We describe a patient who developed a peripheral sensory neuropathy at age 60, which progressed insidiously over the following decade.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During the patient's eighth decade, the patient developed a fluctuant cognitive disturbance with hallucinations before becoming overtly parkinsonian at age 78\u2009years leading to a diagnosis of DLB. At this point, histology slides from a sural nerve biopsy taken at age 72 were re\u2010evaluated and immunohistochemistry demonstrated \u03b1\u2010synuclein deposition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This case provides important in vivo clinical correlation for the Braak hypothesis, extending its scope beyond idiopathic PD. A growing body of evidence supports the \u03b1\u2010synuclein spreading hypothesis that posits the pathologic process begins in the peripheral nerves and spreads trans\u2010synaptically to the CNS in an ascending pattern.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mdc3.13321","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T02:45:21Z","timestamp":1627958721000},"page":"1129-1133","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Braak's Unfinished Hypothesis: A Clinicopathological Case Report of \u03b1\u2010Synuclein Peripheral Neuropathy Preceding Parkinsonism by 20\u2009Years"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2962-0943","authenticated-orcid":false,"given":"Eoghan","family":"Donlon","sequence":"first","affiliation":[{"name":"Department of Neurology Dublin Neurological Institute at the Mater Misericordiae University Hospital  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rionagh","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Neurology Dublin Neurological Institute at the Mater Misericordiae University Hospital  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olwen C.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Neurology Dublin Neurological Institute at the Mater Misericordiae University Hospital  Dublin Ireland"},{"name":"Department of Neurology Johns Hopkins Hospital  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Farrell","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Beaumont Hospital  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaques","family":"Noel","sequence":"additional","affiliation":[{"name":"Department of Medicine for the Elderly Mater Misericordiae University Hospital  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Keogan","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Beaumont Hospital  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"O'Connell","sequence":"additional","affiliation":[{"name":"Department of Radiology Mater Misericordiae University Hospital  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Neurology Dublin Neurological Institute at the Mater Misericordiae University Hospital  Dublin Ireland"},{"name":"Health Affairs University College Dublin  Dublin 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