Evolution and Predictive Role of Plasma Alzheimer's Disease-related Pathological Biomarkers in Parkinson's Disease

Abstract

Plasma Alzheimer's disease-related pathological biomarkers' role in Parkinson's disease (PD) remains unknown. We aimed to determine whether plasma Alzheimer's disease-related biomarkers can predict PD progression. A total of 184 PD patients and 86 healthy controls were included and followed up for 5 years. Plasma phosphorylated tau181 (p-tau181), Aβ40, and Aβ42 were measured at baseline and the 1- and 2-year follow-ups using the Quanterix-single-molecule array. Global cognitive function and motor symptoms were assessed using the Montreal Cognitive Assessment and Unified Parkinson's Disease Rating Scale part III. Genetic analyses were conducted to identify APOE and MAPT genotypes. Plasma p-tau181 levels were higher in PD than healthy controls. APOE-ε4 carriers had lower plasma Aβ42 levels and Aβ42/Aβ40 ratio. The linear mixed-effects models showed that Montreal Cognitive Assessment scores were associated with plasma p-tau181/Aβ42 ratio (β -1.719 [-3.398 to -0.040], p = .045). Higher baseline plasma p-tau181 correlated with faster cognitive decline and motor symptoms deterioration in total patients (β -0.170 [-0.322 to -0.018], p = .029; β 0.329 [0.032 to 0.626], p = .030) and APOE-ε4 carriers (β -0.318 [-0.602 to -0.034], p = .030; β 0.632 [0.017 to 1.246], p = .046), but not in the noncarriers. Higher baseline plasma Aβ40 correlated with faster cognitive decline in total patients (β -0.007 [-0.015 to -0.0001], p = .047) and faster motor symptoms deterioration in total patients (β 0.026 [0.010 to 0.041], p = .001) and APOE-ε4 carriers (β 0.044 [-0.026 to 0.049], p = .020), but not in the noncarriers. The plasma p-tau181/Aβ2 ratio monitors the cognitive status of PD. Higher baseline plasma p-tau181 and Aβ40 predict faster cognitive decline and motor symptoms deterioration in PD, especially in APOE-ε4 carriers.

Keywords: APOE; AD-related pathological biomarkers; Cognitive decline; Parkinson’s disease; Prospective cohort study.