Characterisation of the cellular and transcriptomic profile of neurovascular cells in the ApoE-/- mouse model of atherosclerosis

Systemic atherosclerosis (ATH) is a chronic disease affecting major blood vessels, including cerebral blood supply. Cerebral microvascular dysfunction is implicated in the pathogenesis of dementia, but how systemic vascular disease affects the microvasculature within the central nervous system (CNS) is currently unknown. Evidence of neuroinflammatory changes in the ATH Apolipoprotein E knockout (ApoE- /-) mouse model suggests impairment of the neurovascular unit (NVU). The hypothesis is that ATH is associated with changes in the brain microvasculature, including glial responses that could lead to dysfunction of the NVU and contribute to neurodegeneration. Detailed immunohistological assessment of astrocytes (GFAP), microglia (IBA-1) and endothelial cells (ICAM-1) was performed on two cohorts of ApoE-/- mice fed on a high- fat diet and a normal low-fat diet. Gene expression profiling was also performed on the hippocampus of ApoE-/- mice cohort 2 using laser capture microdissection and microarray analysis.