Progressive cerebrovascular impairment in transgenic Alzheimer’s disease mouse models: a 12-month longitudinal study

Motivation: Understanding how cerebrovascular dysfunction progresses over time alongside pathological changes in Alzheimer's disease (AD) is essential for early detection and intervention strategies. Goal(s): This longitudinal study aims to comprehensively assess alterations in the structure and function of brain blood vessels in transgenic AD mouse models expressing different combinations of AD pathology (Aβ, tau, and Aβ+tau) over 12 months. Approach: We utilized multi-modal perfusion MRI techniques to investigate region-specific vascular changes in the cortex and hippocampus. Results: Cortical thinning was observed in rTg4510 and APP/PS1-rTg4510, with significant vessel size and blood flow changes across groups and timepoints in the cortex and hippocampus. Impact: This study delineates the timeline of cerebrovascular change in AD models, enhancing our ability to interpret in vivo vascular imaging in humans. Future cross-sectional ex vivo microscopy will help validate in vivo MRI measures relevant to AD pathology.