Effects of Alzheimer's genetic risk scores and CSF biomarkers in de novo Parkinson's Disease

Abstract

Coexisting Alzheimer's disease (AD) pathology is common in Parkinson's disease (PD). However, the implications of genetic risk scores (GRS) for AD have not been elucidated in PD. In 413 de novo PD and 195 healthy controls from the Parkinson's Progression Marker Initiative database, the effects of GRS for AD (GRS-AD) and PD (GRS-PD) on the risk of PD and longitudinal CSF biomarkers and clinical outcomes were explored. Higher GRS-PD and lower baseline CSF alpha-synuclein were associated with an increased risk of PD. In the PD group, GRS-AD was correlated positively with CSF p-tau/A beta and negatively with CSF alpha-synuclein. Higher GRS-PD was associated with faster CSF p-tau/A beta increase, and GRS-AD and GRS-PD were interactively associated with CSF alpha-synuclein. In the PD group, higher GRS-AD was associated with poor visuospatial function, and baseline CSF p-tau/A beta was associated with faster cognitive decline. Higher GRS-PD was associated with better semantic fluency and frontal-related cognition and motor function given the same levels of CSF biomarkers and dopamine transporter uptake. Taken together, our results suggest that higher GRS-AD and CSF p-tau/A beta, reflecting AD-related pathophysiology, may be associated with cognitive decline in PD patients.