Delva Aline, Pelletier Amélie, Somerville Emma, Montplaisir Jacques, Gagnon Jean-François, Kollmorgen Gwendlyn, Kam-Thong Tony, Kustermann Thomas, Machado Venissa, Gan-Or Ziv, Postuma Ronald B
The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, QC H3A 2B4, Canada.
Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 2B4, Canada.
Brain. 2025 Jun 3;148(6):2049-2059. doi: 10.1093/brain/awaf003.
Blood-based biomarkers for Alzheimer's disease (AD) pathology have been investigated intensively as markers for AD-related neurodegeneration. Comorbid AD pathology is common in dementia with Lewy bodies (DLB). Accordingly, we hypothesized that plasma biomarkers associated with AD pathology might be useful to predict DLB in a cohort of idiopathic/isolated REM sleep behaviour disorder (iRBD), an incipient synucleinopathy. The aim of this study was to determine whether plasma amyloid-β and pTau181 biomarkers can predict DLB. This longitudinal single-centre (Canada) cohort study included 158 individuals with polysomnography-confirmed iRBD between September 2004 and October 2022, each providing blood plasma samples, who were then offered prospective follow-up. Plasma Aβ40, Aβ42 and pTau181 levels were measured using NeuroToolKit, a prototype assay panel of neurodegeneration (Roche Diagnostics International Ltd). The primary outcome was the association between plasma biomarkers at baseline and eventual development of DLB. Correlations between plasma markers and baseline cognitive tests were assessed. A total of 142 iRBD participants [109 male (77%); mean ± SD, 67.6 ± 8.0 years of age] were included in the final analysis. On prospective follow-up (2.9 ± 2.1 years after sampling), 32 individuals phenoconverted to a defined neurodegenerative syndrome (18 DLB, 13 Parkinson's disease and one multiple system atrophy). The combined phenoconvertor group had lower baseline plasma Aβ42/40 ratio compared with non-phenoconvertors (mean ± SD, 0.103 ± 0.010 versus 0.114 ± 0.012, P < 0.001) and higher pTau181 levels (0.993 ± 0.354 versus 0.784 ± 0.266 pg/ml, P = 0.008). When divided by phenoconversion subtype, significant differences were seen selectively in DLB convertors [Aβ42/40 = 0.101 ± 0.010, difference -0.011, 95% confidence interval (-0.016; -0.005), P < 0.001; pTau181 = 1.144 ± 0.326 pg/ml, difference 0.282 pg/ml, 95% confidence interval (0.146; 0.418), P < 0.001]. Cross-sectional analysis showed that plasma pTau181 (but not Aβ42/40) was correlated with cognitive tests across various domains. Our results indicate that plasma Aβ42/40 ratio and pTau181 can predict conversion to DLB in iRBD.
作为阿尔茨海默病（AD）相关神经退行性变的标志物，基于血液的AD病理生物标志物已得到深入研究。共病AD病理在路易体痴呆（DLB）中很常见。因此，我们假设与AD病理相关的血浆生物标志物可能有助于在一组特发性/孤立性快速眼动睡眠行为障碍（iRBD，一种早期突触核蛋白病）患者中预测DLB。本研究的目的是确定血浆淀粉样蛋白-β和pTau181生物标志物是否能预测DLB。这项纵向单中心（加拿大）队列研究纳入了2004年9月至2022年10月期间158名经多导睡眠图证实的iRBD患者，每人提供血浆样本，随后对其进行前瞻性随访。使用神经工具包（NeuroToolKit，罗氏诊断国际有限公司的神经退行性变原型检测试剂盒）测量血浆Aβ40、Aβ42和pTau181水平。主要结局是基线时血浆生物标志物与DLB最终发生之间的关联。评估了血浆标志物与基线认知测试之间的相关性。最终分析纳入了142名iRBD参与者[109名男性（77%）；平均±标准差，67.6±8.0岁]。在前瞻性随访（采样后2.9±2.1年）中，32人表型转化为明确的神经退行性综合征（18例DLB、13例帕金森病和1例多系统萎缩）。与未表型转化者相比，联合表型转化者组的基线血浆Aβ42/40比值较低（平均±标准差，0.103±0.010对0.114±0.012，P<0.001），pTau181水平较高（0.993±0.354对0.784±0.266 pg/ml，P = 0.008）。按表型转化亚型划分时，仅在DLB转化者中观察到显著差异[Aβ42/40 = 0.101±0.010，差异-0.011，95%置信区间（-0.016；-0.005），P<0.001；pTau181 = 1.144±0.326 pg/ml，差异0.282 pg/ml，95%置信区间（0.146；0.418），P<0.001]。横断面分析表明，血浆pTau181（而非Aβ42/40）与各个领域的认知测试相关。我们的结果表明，血浆Aβ42/40比值和pTau181可以预测iRBD患者向DLB的转化。
