Ye Rong, Kivisäkk Pia, Goodheart Anna, Fatima Hadia, Peterec Erin, Thibault Emma, Properzi Michael, Johnson Keith, Arnold Steven, Gomperts Stephen N
Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Mov Disord. 2025 May 29. doi: 10.1002/mds.30238.
Plasma phosphorylated tau181 (pTau181) is proving to be a useful predictor of Alzheimer's disease (AD). AD co-pathology is frequently observed across the Lewy body disease (LBD) spectrum.
To determine whether pTau181 in LBD is associated with postmortem Alzheimer's disease neuropathologic changes (ADNC) and with antemortem positron emission spectrometry measurements of β-amyloid and tau deposition.
We studied 53 participants with LBD who underwent plasma pTau181 assessment, contrasting them with 129 healthy control participants and 67 participants with AD. Postmortem assessments were conducted on 24 LBD cases. Spearman correlation analyses were used to assess the association between plasma pTau181 and the severity of amyloid deposits, tau accumulation, and neurodegeneration (A/T/N) measured at autopsy or via neuroimaging.
Plasma pTau181 in LBD participants was higher than in healthy participants and lower than in AD participants. Plasma pTau181 in LBD was moderately correlated with Thal stage, Braak neurofibrillary tangle (NFT) stage, and CERAD (Consortium to Establish a Registry for Alzheimer's Disease) scores but not Lewy body Braak stage. Plasma pTau181 was associated with cortical PiB (Pittsburgh Compound-B) retention. Elevated plasma pTau181 levels were associated with greater cortical thinning, particularly in later Braak NFT regions. The addition of plasma pTau181 improved models that included age, sex, and APOE ε4 to detect amyloid and tau positivity.
Plasma pTau181 reflects amyloid and tau pathology but not α-synuclein pathology in LBD. Plasma pTau181 is a useful indicator for neurodegeneration in cortical regions vulnerable to NFT pathology and adds value in identifying AD co-pathology. These findings support plasma pTau181 as a cost-effective screening tool for AD co-pathology in LBD. © 2025 International Parkinson and Movement Disorder Society.
血浆磷酸化tau181（pTau181）已被证明是阿尔茨海默病（AD）的一种有用预测指标。在路易体病（LBD）谱系中经常观察到AD共病病理。
确定LBD患者的pTau181是否与死后阿尔茨海默病神经病理改变（ADNC）以及生前β淀粉样蛋白和tau沉积的正电子发射断层扫描测量结果相关。
我们研究了53例接受血浆pTau181评估的LBD患者，并将他们与129名健康对照者和67例AD患者进行对比。对24例LBD病例进行了死后评估。采用Spearman相关性分析来评估血浆pTau181与尸检或通过神经影像学测量的淀粉样蛋白沉积、tau积累和神经退行性变（A/T/N）严重程度之间的关联。
LBD患者的血浆pTau181高于健康参与者，低于AD患者。LBD患者的血浆pTau181与Thal分期、Braak神经原纤维缠结（NFT）分期和CERAD（阿尔茨海默病注册协会）评分中度相关，但与路易体Braak分期无关。血浆pTau181与皮质PiB（匹兹堡化合物B）滞留有关。血浆pTau181水平升高与更大程度的皮质变薄有关，特别是在后期Braak NFT区域。加入血浆pTau181可改善包含年龄、性别和APOE ε4的模型以检测淀粉样蛋白和tau阳性。
血浆pTau181反映LBD中的淀粉样蛋白和tau病理，但不反映α-突触核蛋白病理。血浆pTau181是易患NFT病理的皮质区域神经退行性变的有用指标，并在识别AD共病病理方面具有附加价值。这些发现支持血浆pTau181作为LBD中AD共病病理的一种经济有效的筛查工具。© 2025国际帕金森和运动障碍协会。
