The relevance of cerebrospinal fluid α-synuclein levels to sporadic and familial Alzheimer’s disease

Autor: Daniel Twohig, Elena Rodriguez-Vieitez, Sigrid B. Sando, Guro Berge, Camilla Lauridsen, Ina Møller, Gøril R. Grøntvedt, Geir Bråthen, Kalicharan Patra, Guojun Bu, Tammie L. S. Benzinger, Celeste M. Karch, Anne Fagan, John C. Morris, Randall J. Bateman, Agneta Nordberg, Linda R. White, Henrietta M. Nielsen, for the Dominantly Inherited Alzheimer Network (DIAN)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Acta Neuropathologica Communications, Vol 6, Iss 1, Pp 1-19 (2018)
ISSN: 2051-5960
DOI: 10.1186/s40478-018-0624-z
Popis: Accumulating evidence demonstrating higher cerebrospinal fluid (CSF) α-synuclein (αSyn) levels and αSyn pathology in the brains of Alzheimer’s disease (AD) patients suggests that αSyn is involved in the pathophysiology of AD. To investigate whether αSyn could be related to specific aspects of the pathophysiology present in both sporadic and familial disease, we quantified CSF levels of αSyn and assessed links to various disease parameters in a longitudinally followed cohort (n = 136) including patients with sporadic mild cognitive impairment (MCI) and AD, and in a cross-sectional sample from the Dominantly Inherited Alzheimer’s Network (n = 142) including participants carrying autosomal dominant AD (ADAD) gene mutations and their non-mutation carrying family members. Our results show that sporadic MCI patients that developed AD over a period of two years exhibited higher baseline αSyn levels (p = 0.03), which inversely correlated to their Mini-Mental State Examination scores, compared to cognitively normal controls (p = 0.02). In the same patients, there was a dose-dependent positive association between CSF αSyn and the APOEε4 allele. Further, CSF αSyn levels were higher in symptomatic ADAD mutation carriers versus non-mutation carriers (p = 0.03), and positively correlated to the estimated years from symptom onset (p = 0.05) across all mutation carriers. In asymptomatic (Clinical Dementia Rating
Databáze: OpenAIRE
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