Tau profiling across Alzheimer’s disease staging reveals vulnerability to disease pathophysiology

IF 8.6 1区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2025-04-25 DOI:10.1007/s00259-025-07257-4

Gleb Bezgin, Tharick A. Pascoal, Joseph Therriault, Firoza Z. Lussier, Stijn Servaes, Min Su Kang, Mélissa Savard, Cécile Tissot, Jenna Stevenson, Yi-Ting Wang, Julie Ottoy, Nesrine Rahmouni, Jaime Fernandez-Arias, Seyyed Ali Hosseini, Étienne Aumont, Brandon Hall, Nina Margherita Poltronetti, Vanessa Pallen, Andréa Lessa Benedet, Nicholas J. Ashton, Kaj Blennow, Henrik Zetterberg, Thomas K. Karikari, Tatsuhiro Terada, Mira Chamoun, Sulantha Mathotaarachchi, Arthur Cassa Macedo, Alyssa Stevenson, Peter Kunach, Gassan Massarweh, Paolo Vitali, Jean-Paul Soucy, Yasser Iturria-Medina, Serge Gauthier, Pedro Rosa-Neto

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引用次数: 0

Abstract

Background

Inter-individual variability in tau topography challenges the propagation hypothesis of tau aggregates.

Methods

To address this gap, we propose the Manifold Component Analysis (MCA), for identifying pseudo-continuous profiles informed by the spatial continuity of stage regions.

Results

Longitudinal and cross-sectional MCA in large aging cohort identified individual profiles (N = 753) expressing tau load in the entorhinal, limbic and neocortical regions. Using these profiles, we found neuropsychological and blood-based milestones of early and late disease stages. Finally, we also found evidence of rapid tau load increases and cognitive decline centered at the early-to-mid neocortical stages of Alzheimer’s disease.

Conclusions

Stage system based on tau load and spreading profiles across cortical areas provide a compelling framework for inferring pathophysiological prognosis in Alzheimer’s disease.

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跨阿尔茨海默病分期的Tau谱分析揭示了疾病病理生理学的脆弱性

tau地形的个体间变异挑战了tau聚集体的传播假说。为了解决这一差距，我们提出了流形分量分析（MCA），用于识别由阶段区域的空间连续性通知的伪连续剖面。结果纵向和横断面MCA在大型老龄化队列中确定了在内嗅、边缘和新皮质区域表达tau负荷的个体特征（N = 753）。利用这些资料，我们发现了疾病早期和晚期的神经心理学和血液里程碑。最后，我们还发现在阿尔茨海默病的早期到中期，tau负荷快速增加和认知能力下降的证据。结论基于tau负荷和皮层区分布谱的分期系统为推断阿尔茨海默病的病理生理预后提供了一个令人信服的框架。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Nuclear Medicine and Molecular Imaging 医学-核医学

CiteScore

15.60

自引率

9.90%

发文量

392

审稿时长

3 months

期刊介绍： The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.