Hiraga Keita, Hattori Makoto, Satake Yuki, Tamakoshi Daigo, Fukushima Taiki, Uematsu Takashi, Tsuboi Takashi, Sato Maki, Yokoi Katsunori, Suzuki Keisuke, Arahata Yutaka, Washimi Yukihiko, Hori Akihiro, Yamamoto Masayuki, Shimizu Hideaki, Wakai Masakazu, Tatebe Harutsugu, Tokuda Takahiko, Nakamura Akinori, Niida Shumpei, Katsuno Masahisa
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Neurology, Daido Hospital, Nagoya, Japan.
NPJ Parkinsons Dis. 2024 Jul 31;10(1):135. doi: 10.1038/s41531-024-00745-8.
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.
共病的阿尔茨海默病（AD）神经病理学在路易体病（LBD）中很常见；然而，LBD前驱期的AD共病情况仍不清楚。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共病情况。纳入了PD患者（PD组，n = 84）、DLB患者（DLB组，n = 16）以及有≥2种前驱症状的LBD个体（高危组，n = 82）和无前驱症状的LBD个体（低危组，n = 37）。使用免疫沉淀-质谱分析法测量血浆淀粉样β蛋白（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组和DLB组的血浆p-tau181水平高于低危组。DLB组的Aβ复合物水平高于高危组。高危组中与AD相关的生物标志物水平未升高。高危组、PD组和DLB组的NfL水平高于低危组。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、运动功能和非运动症状相关。在高危组中，NfL与间碘苄胍闪烁显像异常相关。PD组和DLB组存在共病的AD神经病理学，尽管在前驱期不存在。即使血浆中与AD相关的生物标志物水平未升高，但血浆NfL水平升高可能表明LBD前驱期存在aSyn诱导的神经变性。
