Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Alzheimers Dement. 2024 Jun;20(6):3889-3905. doi: 10.1002/alz.13777. Epub 2024 Apr 21.
We investigate pathological correlates of plasma phosphorylated tau 181 (p-tau), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) across a clinically diverse spectrum of neurodegenerative disease, including normal cognition (NormCog) and impaired cognition (ImpCog).
Participants were NormCog (n = 132) and ImpCog (n = 461), with confirmed β-amyloid (Aβ+/-) status (cerebrospinal fluid, positron emission tomography, autopsy) and single molecule array plasma measurements. Logistic regression and receiver operating characteristic (ROC) area under the curve (AUC) tested how combining plasma analytes discriminated Aβ+ from Aβ-. Survival analyses tested time to clinical dementia rating (global CDR) progression.
Multivariable models (p-tau+GFAP+NfL) had the best performance to detect Aβ+ in NormCog (ROCAUC = 0.87) and ImpCog (ROCAUC = 0.87). Survival analyses demonstrated that higher NfL best predicted faster CDR progression for both Aβ+ (hazard ratio [HR] = 2.94; p = 8.1e-06) and Aβ- individuals (HR = 3.11; p = 2.6e-09).
Combining plasma biomarkers can optimize detection of Alzheimer's disease (AD) pathology across cognitively normal and clinically diverse neurodegenerative disease.
Participants were clinically heterogeneous, with autopsy- or biomarker-confirmed Aβ. Combining plasma p-tau, GFAP, and NfL improved diagnostic accuracy for Aβ status. Diagnosis by plasma biomarkers is more accurate in amnestic AD than nonamnestic AD. Plasma analytes show independent associations with tau PET and post mortem Aβ/tau. Plasma NfL predicted longitudinal cognitive decline in both Aβ+ and Aβ- individuals.
我们研究了在包括认知正常（NormCog）和认知障碍（ImpCog）在内的神经退行性疾病的广泛临床谱系中，血浆磷酸化 tau181（p-tau）、神经胶质纤维酸性蛋白（GFAP）和神经丝轻链（NfL）的病理相关性。
参与者为 NormCog（n=132）和 ImpCog（n=461），并经β-淀粉样蛋白（Aβ+/-）状态（脑脊液、正电子发射断层扫描、尸检）和单分子阵列血浆测量证实。逻辑回归和接收器操作特性（ROC）曲线下面积（AUC）检验了组合血浆分析物如何区分 Aβ+和 Aβ-。生存分析检验了临床痴呆评定（global CDR）进展的时间。
多变量模型（p-tau+GFAP+NfL）在 NormCog（ROCAUC=0.87）和 ImpCog（ROCAUC=0.87）中具有最佳的性能来检测 Aβ+。生存分析表明，较高的 NfL 最佳预测了 Aβ+（风险比[HR]=2.94；p=8.1e-06）和 Aβ-个体（HR=3.11；p=2.6e-09）更快的 CDR 进展。
组合血浆生物标志物可以优化对认知正常和临床多样化神经退行性疾病中阿尔茨海默病（AD）病理的检测。
参与者在认知上存在异质性，且具有经尸检或生物标志物证实的 Aβ。组合血浆 p-tau、GFAP 和 NfL 提高了 Aβ 状态的诊断准确性。与非遗忘性 AD 相比，血浆生物标志物诊断更准确。血浆分析物与 tau PET 和死后 Aβ/tau 具有独立关联。在 Aβ+和 Aβ-个体中，血浆 NfL 均预测了纵向认知下降。
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