Brown Christopher A, Cousins Katheryn A Q, Korecka Magdalena, McGrew Emily, Chen-Plotkin Alice, Detre John A, McMillan Corey T, Lee Edward B, Das Sandhitsu R, Mechanic-Hamilton Dawn, Yushkevich Paul A, Nasrallah Ilya M, Shaw Leslie M, Wolk David A
Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
medRxiv. 2025 Sep 7:2025.09.04.25334935. doi: 10.1101/2025.09.04.25334935.
To compare PET and plasma-based temporal modeling of amyloid and tau biomarkers in Alzheimer's disease.
Longitudinal amyloid PET, F-flortaucipir tau-PET, and Fujirebio Lumipulse plasma p-tau from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and University of Pennsylvania Alzheimer's Disease Research Center (Penn ADRC) were used to generate biomarker trajectory models using Sampled Iterative Local Approximation (SILA). SILA models using plasma p-tau were compared to amyloid and tau PET-based models to estimate tau onset age (ETOA) and estimate amyloid onset age (EAOA), and factors influencing ETOA and time from ETOA to dementia were evaluated for PET and plasma-based models.
Plasma-based models generated similar results to PET for EAOA and ETOA, with stronger model agreement for ETOA than EAOA. Accuracy of estimated onset age compared to actual onset age was high within modality with slightly greater error when comparing across modalities (i.e. plasma to PET). For both plasma and PET models, earlier ETOA was associated with younger EAOA, female sex, and ≥1 ApoE ε4 allele. Earlier dementia onset after ETOA was associated with later ETOA for both plasma and PET models, while male sex was associated with shorter tau to dementia gap in plasma models.
Temporal modeling of plasma biomarkers provides comparable information to PET-based models, particularly for tau onset age. Plasma-based temporal modeling can serve as a widely accessible tool for clinical assessment of biological disease duration that places the patient on the disease timeline, which may allow for improved discussion of prognosis and treatment decisions.
比较正电子发射断层扫描（PET）与基于血浆的阿尔茨海默病淀粉样蛋白和tau生物标志物的时间建模。
利用阿尔茨海默病神经影像倡议（ADNI）和宾夕法尼亚大学阿尔茨海默病研究中心（Penn ADRC）的纵向淀粉样蛋白PET、F-氟代托卡朋tau-PET以及富士瑞必欧Lumipulse血浆p-tau，采用采样迭代局部近似法（SILA）生成生物标志物轨迹模型。将基于血浆p-tau的SILA模型与基于淀粉样蛋白和tau PET的模型进行比较，以估计tau发病年龄（ETOA）和淀粉样蛋白发病年龄（EAOA），并评估PET和基于血浆的模型中影响ETOA以及从ETOA到痴呆症的时间的因素。
基于血浆的模型在EAOA和ETOA方面产生了与PET相似的结果，ETOA的模型一致性比EAOA更强。与实际发病年龄相比，估计发病年龄在各模态内的准确性较高，跨模态比较（即血浆与PET）时误差略大。对于血浆和PET模型，较早的ETOA与较年轻的EAOA、女性以及≥一个载脂蛋白Eε4等位基因相关。在血浆和PET模型中，ETOA后较早的痴呆症发病均与较晚的ETOA相关，而男性在血浆模型中与从tau到痴呆症的间隔时间较短相关。
血浆生物标志物的时间建模提供了与基于PET的模型相当的信息，特别是对于tau发病年龄。基于血浆的时间建模可作为一种广泛可用的工具，用于临床评估将患者置于疾病时间线上的生物疾病持续时间，这可能有助于改善对预后和治疗决策的讨论。
