Bezgin Gleb, Pascoal Tharick A, Therriault Joseph, Lussier Firoza Z, Servaes Stijn, Kang Min Su, Savard Mélissa, Tissot Cécile, Stevenson Jenna, Wang Yi-Ting, Ottoy Julie, Rahmouni Nesrine, Fernandez-Arias Jaime, Hosseini Seyyed Ali, Aumont Étienne, Hall Brandon, Poltronetti Nina Margherita, Pallen Vanessa, Benedet Andréa Lessa, Ashton Nicholas J, Blennow Kaj, Zetterberg Henrik, Karikari Thomas K, Terada Tatsuhiro, Chamoun Mira, Mathotaarachchi Sulantha, Macedo Arthur Cassa, Stevenson Alyssa, Kunach Peter, Massarweh Gassan, Vitali Paolo, Soucy Jean-Paul, Iturria-Medina Yasser, Gauthier Serge, Rosa-Neto Pedro
Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, McGill University, Montréal, QC, Canada.
Neuroinformatics for Personalized Medicine lab, Montreal Neurological Institute, McGill University, Montréal, QC, Canada.
Eur J Nucl Med Mol Imaging. 2025 Apr 25. doi: 10.1007/s00259-025-07257-4.
Inter-individual variability in tau topography challenges the propagation hypothesis of tau aggregates.
To address this gap, we propose the Manifold Component Analysis (MCA), for identifying pseudo-continuous profiles informed by the spatial continuity of stage regions.
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.
Stage system based on tau load and spreading profiles across cortical areas provide a compelling framework for inferring pathophysiological prognosis in Alzheimer's disease.
tau蛋白分布的个体间差异对tau蛋白聚集体的传播假说提出了挑战。
为填补这一空白，我们提出了流形成分分析（MCA），用于识别由分期区域的空间连续性所提供信息的伪连续图谱。
在大型老年队列中的纵向和横断面MCA识别出了在内嗅区、边缘区和新皮质区表达tau蛋白负荷的个体图谱（N = 753）。利用这些图谱，我们发现了疾病早期和晚期的神经心理学及血液学标志物。最后，我们还发现了以阿尔茨海默病早期至中期新皮质阶段为中心的tau蛋白负荷快速增加和认知衰退的证据。
基于tau蛋白负荷和跨皮质区域传播图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有说服力的框架。
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