Interaction of CSF alpha-synuclein and amyloid beta in cognition and cortical atrophy

Abstract

Introduction: Lewy body-related pathology is commonly observed at autopsy in individuals with dementia, but in vivo biomarkers for alpha-synucleinopathy are lacking. Methods: Baseline cerebrospinal fluid (CSF) biomarkers, polygenic risk score (PRS) for Parkinson's disease (PRS-PD) and Alzheimer's disease (PRS-AD), longitudinal cognitive scores, and magnetic resonance imaging were measured in 217 participants from the Alzheimer's Disease Neuroimaging Initiative. Linear mixed models were used to find the relationship of CSF biomarkers and the PRS with cognition and cortical atrophy. Results: Higher PRS-PD and PRS-AD were associated with lower CSF alpha-synuclein and amyloid beta (A beta), respectively. Lower CSF alpha-synuclein and the interaction of CSF alpha-synuclein and A beta were associated with lower cognitive scores and global cortical atrophy most prominently in the occipital cortex. Discussion: Lower CSF alpha-synuclein could be a biomarker for alpha-synucleinopathy, and the simultaneous evaluation of CSF biomarkers for AD and CSF alpha-synuclein could reveal the independent and interactive effects on cognition and cortical atrophy.