Abstract 101: ApoE4 Disrupts Cerebrovascular Microcirculation and Undermines White Matter Integrity and Cognitive Function

Background: Small vessel disease leading to subcortical white matter lesions (WML) is the major cause of vascular cognitive impairment. The apolipoprotein E4 (ApoE4) allele, a well-known risk factor for Alzheimer’s disease, is also a risk factor for WML, but the mechanisms of the effect remain unclear. We set out to determine whether the ApoE4 genotype disrupts the cerebral microcirculation and promotes WML and cognitive impairment. Methods: We studied male ApoE4 targeted replacement mice (ApoE4-TR; age 3-4 months). ApoE3 (ApoE3-TR) were used as controls. Cerebral blood flow (CBF) was assessed by ASL-MRI; the CBF increase induced by whisker stimulation (WS) or the endothelium-dependent agent acetylcholine (ACh) was assessed in cranial window preparations by laser-Doppler flowmetry. The corpus callosum (CC) microcirculation was examined by three-photon microscopy (3PM). Bilateral carotid artery stenosis (BCAS) was induced with 0.18 mm microcoils. WML and cognition were tested 4 weeks after BCAS. Results: I...