•Cerebral microvascular disease (CMD) is a leading cause of age-related cognitive decline and a major risk factor for stroke. Emerging evidence links CMD to the development and progression of Alzheimer’s disease (AD).

•Brain endothelial cells are the primary site of pathology in CMD

•Systematic identification and measurement of dysfunction molecular pathways in brain endothelia is challenging as these cells are difficult to isolate, resistant to traditional viral transduction approaches, and single-cell technologies require extensive tissue processing that can limit deep molecular profiling.

•To address this, we developed viral translating ribosome affinity purification (vTRAP) to profile endothelial cells in healthy and diseased states.

•This platform allows systematic comparisons of endothelial gene expression across species, highlighting early molecular changes in CMD and AD-related dementias (ADRDs).

•We will focus on endothelial contributions in models of tau, amyloid-beta, and hypertension