Comorbid Alzheimer’s disease (AD) neuropathology is common in Lewy body disease (LBD); however, AD comorbidity in the prodromal phase of LBD remains unclear. This study investigated AD comorbidity in the prodromal and symptomatic phases of LBD by analyzing plasma biomarkers in patients with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) and individuals at risk of LBD (NaT-PROBE cohort). Patients with PD (PD group, n = 84) and DLB (DLB group, n = 16) and individuals with LBD with ≥ 2 (high-risk group, n = 82) and without (low-risk group, n = 37) prodromal symptoms were enrolled. Plasma amyloid-beta (Aβ) composite was measured using immunoprecipitation-mass spectrometry assays. Plasma phosphorylated tau 181 (p-tau181), neurofilament light chain (NfL), and alpha-synuclein (aSyn) were measured using a single-molecule array. Plasma p-tau181 levels were higher in the PD and DLB groups than in the low-risk group. Aβ composite level was higher in the DLB group than in the high-risk group. AD-related biomarker levels were not elevated in the high-risk group. NfL levels were higher in the high-risk, PD, and DLB groups than in the low-risk group. In the PD group, Aβ composite was associated with cognitive function, p-tau181 with motor function and non-motor symptoms, and NfL with cognitive and motor functions and non-motor symptoms. In the high-risk group, NfL was associated with metaiodobenzylguanidine scintigraphy abnormalities. The PD and DLB groups exhibited comorbid AD neuropathology, though not in the prodromal phase. Elevated plasma NfL levels, even without elevated AD-related plasma biomarker levels, may indicate aSyn-induced neurodegeneration in the LBD prodromal phase.

路易体病 (LBD) 中常见阿尔茨海默病 (AD) 神经病理学共病；然而，LBD 前驱期的 AD 合并症仍不清楚。本研究通过分析帕金森病 (PD) 和路易体痴呆 (DLB) 患者以及有 LBD 风险的个体（NaT-PROBE 队列）的血浆生物标志物，调查了 LBD 前驱期和症状期的 AD 合并症。 PD 患者（PD 组， n = 84）和 DLB 患者（DLB 组， n = 16）以及 LBD ≥ 2 的个体（高风险组， n = 82）和无 LBD 的个体（低风险组， n = 37）纳入前驱症状。使用免疫沉淀-质谱分析法测量血浆淀粉样蛋白-β (Aβ) 复合物。使用单分子阵列测量血浆磷酸化 tau 181 (p-tau181)、神经丝轻链 (NfL) 和 α-突触核蛋白 (aSyn)。 PD 和 DLB 组的血浆 p-tau181 水平高于低风险组。 DLB组的Aβ复合水平高于高危组。高危组中 AD 相关生物标志物水平并未升高。高风险组、PD 组和 DLB 组的 NfL 水平高于低风险组。在PD组中，Aβ复合物与认知功能相关，p-tau181与运动功能和非运动症状相关，NfL与认知和运动功能以及非运动症状相关。在高危组中，NfL 与间碘苄胍闪烁扫描异常相关。 PD 和 DLB 组表现出共病 AD 神经病理学，尽管不是在前驱期。即使 AD 相关血浆生物标志物水平没有升高，血浆 NfL 水平升高也可能表明 LBD 前驱期 aSyn 诱导的神经变性。