Mesoscopic vascular alterations in Alzheimer's disease

作者：Mackenzie Hyman, Shuaibin Chang, Dayang Gong, Etienne Chollet, Jiarui Yang, Anna Novoseltseva, Ayman A Abdelhakeem, Gϋlce Kϋreli, Shuying Li, J. S. Bevan, Janice Weinberg, Patrick R. Hof, Ann C. McKee, Irving J. Bigio, David A. Boas, Bertrand R. Huber, Hui Wang · 发表于：Alzheimer s & Dementia · 年份：2025 · DOI：10.1002/alz.70907 · 被引用次数：3 · 研究领域：Optical Coherence Tomography Applications、Cerebrospinal fluid and hydrocephalus、Dementia and Cognitive Impairment Research

INTRODUCTION: Cerebrovascular alterations are associated with the pathology of Alzheimer's disease (AD). Yet, the role of these alterations is not fully understood, partly due to a paucity of data from mesoscopic vasculature (24-240 µm diameter). METHODS: We used label-free, serial-sectioning optical coherence tomography to reconstruct mesoscopic cerebrovasculature of the dorsolateral prefrontal cortex (DLPFC) samples from AD and control subjects. We quantified three-dimensional alterations to the vascular networks and measured the correlations between vascular alterations and deposits of amyloid β protein (Aβ) and phosphorylated tau protein (p-tau). RESULTS: The AD group had significantly reduced volume fraction, vessel length density, and branch density. There were negative trends between a subset of the vascular metrics and the density of Aβ and p-tau. DISCUSSION: AD samples in DLPFC present with significant mesoscopic cerebrovasculature alterations. This insight helps close the knowledge gap between micro- and macroscopic cerebrovascular pathologies. HIGHLIGHTS: Volumetric imaging of mesoscopic cerebrovasculature with serial-sectioning optical coherence tomography (OCT). Vascular metrics: volume fraction, length density, branch density, and tortuosity. Human ex vivo samples from dorsolateral prefrontal cortex (Alxzheimer's disease [AD] and controls). Compared to controls, AD had reduced vascularity. Serial-sectioning OCT provides novel insights into mesoscopic cerebrovasc...