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Patterns and stages of α-synucleinopathy: Relevance in a population-based cohort

Lookup NU author(s): Professor Carol Brayne, Professor Ian McKeith


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BACKGROUND: It is proposed that α-synucleinopathy (AS) initially affects the medulla oblongata and progresses to more rostral brain areas in a hierarchical sequence ("Braak hypothesis"). Predominant involvement of the amygdala is also described. This study examines the applicability of these patterns, and their relationship to Alzheimer disease (AD) pathology, in brains of a population-based donor cohort. METHODS: Brains donated in two of six Cognitive Function and Ageing Study cohorts (Cambridgeshire and Nottingham) were examined. More than 80% were older than 80 years at death. The respondents were evaluated prospectively in life for cognitive decline and dementia. Immunocytochemistry for tau and α-synuclein was carried out in 208 brains to establish Braak stage and the pattern and severity of AS. RESULTS: Seventy-six brains showed Lewy bodies. Half (51%) conformed to the Braak hypothesis while 17% had pathology in a higher region which was absent in a lower region. A further 29% showed amygdala-predominant pathology. Six brains showed predominant neocortical pathology with minimal pathology in amygdala or substantia nigra. The stage of AD pathology was not associated with particular patterns of AS. CONCLUSION: α-Synucleinopathy (AS) is common in older people, and frequently associated with Alzheimer disease-type pathology. Although half of brains corresponded to the Braak hypothesis, and 29% to amygdala-predominant AS, there were a high proportion of cases which did not fit a staging system. An unexpectedly high proportion with a cortical form of Lewy body disease was identified. ©2008AAN Enterprises, Inc.

Publication metadata

Author(s): Zaccai J, Brayne C, McKeith I, Matthews F, Ince PG

Publication type: Article

Publication status: Published

Journal: Neurology

Year: 2008

Volume: 70

Issue: 13

Pages: 1042-1048

ISSN (print): 0028-3878

ISSN (electronic): 1526-632X

Publisher: Lippincott Williams & Wilkins


DOI: 10.1212/01.wnl.0000306697.48738.b6

PubMed id: 18362284


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Funder referenceFunder name
G0400074Medical Research Council
G0502157Medical Research Council
G9901400Medical Research Council
G0300126Medical Research Council
MC_U105292687Medical Research Council