Effects of α-synuclein pathology on synaptic dysfunction and clinical outcomes in normal aging.
Effects of α-synuclein pathology on synaptic dysfunction and clinical outcomes in normal aging.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Palo Alto, US · Author affiliation
Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.Location evidence
US · Author affiliation · country only
Wu Tsai Neurosciences Institute, Stanford University, Stanford, California, USA.Location evidence
New York City, US · Author affiliation
Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.Location evidence
Davis, US · Author affiliation
Department of Radiology, University of California Davis, Sacramento, California, USA.Location evidence
Sacramento, US · Author affiliation
Department of Radiology, University of California Davis, Sacramento, California, USA.Location evidence
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Original abstract
INTRODUCTION: α-Synuclein is the hallmark pathology of Parkinson's disease and dementia with Lewy bodies, described together as Lewy body disease (LBD). We investigated effects of α-syn biomarker positivity in clinically unimpaired (CU) individuals. METHODS: We assessed α-syn status (α-syn ±) in 269 CU individuals using a cerebrospinal fluid (CSF) seed amplification assay (SAA). Fifty-six participants with AD and 85 LBD spectrum participants were included for comparison. We compared α-syn SAA results with demographics, fluid biomarkers, cognitive performance, and clinical measures. RESULTS: α -Syn positivity was detected in 9% of CU individuals, a lower rate than in clinically impaired participants with AD (16%) and LBD diagnoses (81%). Compared to α-syn-, α-syn+ CU individuals were older, showed lower synaptic integrity, performed worse on tests of executive function and working memory, and reported more LBD-related non-motor symptoms. DISCUSSION: Further work is needed to understand the timeline of neural and clinical changes in α-syn+ CU individuals and heterogeneity in disease progression.