来自活体扩散磁共振成像的灰质微观结构反映了阿尔茨海默病的死后神经病理学严重程度和临床进展。

Gray matter microstructure from in-vivo diffusion MRI reflects post-mortem neuropathology severity and clinical progression of Alzheimer's disease.

作者信息

Alasmar Zaki, Tremblay Cécilia, Moqadam Roqaie, Serrano Geidy E, Beach Thomas G, Atri Alizera, Su Yi, Zeighami Yashar, Dadar Mahsa

机构信息

Cerebral Imaging Centre, Douglas Mental Health University Institute, Montréal, Québec, Canada, H4H 1R3.

Department of Psychiatry, McGill University, Montréal, Québec, Canada, H4H 1R3 6875 Boulevard LaSalle Montréal, QC H4H 1R3.

出版信息

medRxiv. 2025 Jun 4:2025.05.30.25328630. doi: 10.1101/2025.05.30.25328630.

DOI:10.1101/2025.05.30.25328630

PMID:40502575

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12154994/

Abstract

INTRODUCTION

Diffusion-weighted imaging derived mean diffusivity (MD) correlates with Alzheimer's disease biomarkers, yet its neuropathological correlates remain unclear.

METHODS

Diffusion-weighted imaging, postmortem neuropathology, and cognitive performance data were obtained from the National Alzheimer's Coordinating Center (N=97), Alzheimer's Disease Neuroimaging Initiative (N=21), and Arizona Study of Aging and Neurodegenerative Disorders (N=15). We examined MD associations with neuropathology, cognitive decline, and expression profiles of AD-implicated genes.

RESULTS

Results revealed two latent variables-one linked to amyloid/tau, the other to vascular pathology-explaining 70% and 16% of MD-pathology covariance, respectively. Higher MD correlated with worse cognitive performance, both cross-sectionally and up to 14 years prior to death. MD was regionally associated with Thal phase, neuritic plaque density, Braak stage (temporal/limbic), and infarcts (thalamus), and reflected gene expression patterns related to AD.

DISCUSSION

In vivo MD captures distinct AD-related pathologies across brain regions and relates to cognitive trajectories and gene expression.

摘要

引言

扩散加权成像衍生的平均扩散率（MD）与阿尔茨海默病生物标志物相关，但其神经病理学相关性仍不清楚。

方法

从国家阿尔茨海默病协调中心（N = 97）、阿尔茨海默病神经影像学倡议（N = 21）和亚利桑那衰老与神经退行性疾病研究（N = 15）获取扩散加权成像、尸检神经病理学和认知表现数据。我们研究了MD与神经病理学、认知衰退以及阿尔茨海默病相关基因表达谱的关联。

结果

结果揭示了两个潜在变量——一个与淀粉样蛋白/ tau相关，另一个与血管病理学相关——分别解释了MD - 病理学协方差的70%和16%。较高的MD与较差的认知表现相关，无论是在横断面还是在死亡前长达14年的时间里。MD在区域上与Thal分期、神经炎性斑块密度、Braak分期（颞叶/边缘系统）和梗死灶（丘脑）相关，并反映了与阿尔茨海默病相关的基因表达模式。