Department of Neurology, Laboratory of Neurodegenerative Disorders, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
J Gerontol A Biol Sci Med Sci. 2023 Dec 1;78(12):2203-2213. doi: 10.1093/gerona/glad189.
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.
血浆阿尔茨海默病相关病理生物标志物在帕金森病（PD）中的作用尚不清楚。我们旨在确定血浆阿尔茨海默病相关生物标志物是否可预测 PD 的进展。共纳入 184 名 PD 患者和 86 名健康对照者，并进行了 5 年的随访。使用 Quanterix 单分子阵列在基线以及 1 年和 2 年的随访时测量血浆磷酸化 tau181（p-tau181）、Aβ40 和 Aβ42。使用蒙特利尔认知评估和统一帕金森病评定量表第 III 部分评估整体认知功能和运动症状。进行了基因分析以鉴定 APOE 和 MAPT 基因型。PD 患者的血浆 p-tau181 水平高于健康对照组。APOE-ε4 携带者的血浆 Aβ42 水平和 Aβ42/Aβ40 比值较低。线性混合效应模型显示，蒙特利尔认知评估评分与血浆 p-tau181/Aβ42 比值相关（β-1.719[-3.398 至-0.040]，p=0.045）。较高的基线血浆 p-tau181 与总患者的认知能力下降和运动症状恶化呈正相关（β-0.170[-0.322 至-0.018]，p=0.029；β0.329[0.032 至 0.626]，p=0.030）和 APOE-ε4 携带者（β-0.318[-0.602 至-0.034]，p=0.030；β0.632[0.017 至 1.246]，p=0.046），而非携带者则没有。较高的基线血浆 Aβ40 与总患者的认知能力下降（β-0.007[-0.015 至-0.0001]，p=0.047）和总患者的运动症状恶化（β0.026[0.010 至 0.041]，p=0.001）呈正相关，与 APOE-ε4 携带者（β0.044[-0.026 至 0.049]，p=0.020），而非携带者则没有。血浆 p-tau181/Aβ2 比值可监测 PD 的认知状态。较高的基线血浆 p-tau181 和 Aβ40 可预测 PD 患者的认知能力下降和运动症状恶化，尤其是 APOE-ε4 携带者。
