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

Plasma Alzheimer's disease (AD)-related pathological biomarkers' role in Parkinson's disease (PD) remains unknown. We aimed to determine whether plasma AD-related biomarkers can predict PD progression. A total of 184 PD patients and 86 healthy controls (HCs) were included and followed up for five years. Plasma p-tau181, Aβ40, and Aβ42 were measured at baseline and the 1- and 2-year follow-ups using the Quanterix-SIMOA. Global cognitive function and motor symptoms were assessed using the Montreal Cognitive Assessment (MoCA) and Unified Parkinson's Disease Rating Scale part III (UPDRS-III). Genetic analyses were conducted to identify APOE and MAPT genotypes. Plasma p-tau181 levels were higher in PD than HCs. APOE-ε4 carriers had lower plasma Aβ42 levels and Aβ42/Aβ40 ratio. The linear mixed-effects models showed that MoCA scores were associated with plasma p-tau181/Aβ42 ratio (β -1.719 [-3.398--0.040], p= 0.045). Higher baseline plasma p-tau181 correlated with faster cognitive decline and motor symptoms deterioration in total patients (β -0.170 [-0.322--0.018], p=0.029; β 0.329 [0.032-0.626], p=0.030) and APOE-ε4 carriers (β -0.318 [-0.602--0.034], p=0.030; β 0.632 [0.017-1.246], p=0.046), but not in the non-carriers. Higher baseline plasma Aβ40 correlated with faster cognitive decline in total patients (β -0.007 [-0.015--0.0001], p=0.047) and faster motor symptoms deterioration in total patients (β 0.026 [0.010-0.041], p=0.001) and APOE-ε4 carriers (β 0.044 [-0.026-0.049], p=0.020), but not in the non-carriers. 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.