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

Introduction: Lewy body-related pathology is commonly observed at autopsy in individuals with dementia, but in vivo biomarkers for α-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 α-synuclein and amyloid beta (Aβ), respectively. Lower CSF α-synuclein and the interaction of CSF α-synuclein and Aβ were associated with lower cognitive scores and global cortical atrophy most prominently in the occipital cortex. Discussion: Lower CSF α-synuclein could be a biomarker for α-synucleinopathy, and the simultaneous evaluation of CSF biomarkers for AD and CSF α-synuclein could reveal the independent and interactive effects on cognition and cortical atrophy.ope