Aberrant vascular architecture in the hippocampus correlates with tau burden in mild cognitive impairment and Alzheimer's disease

Abstract

Cerebrovascular dysfunction is a significant contributor to Alzheimer’s disease (AD) progression. AD mouse modelsshow altered capillary morphology, density, and diminished blood flow in areas of tau and beta-amyloid accumulation. Thepurpose of this study was to examine alterations in vascular structure and their contributions to perfusion deficits in thehippocampus in AD and mild cognitive impairment (MCI). Seven individuals with AD and MCI (1 AD/6 MCI), ninecognitively intact older healthy adults, and seven younger healthy adults underwent pseudo-continuous arterial spinlabeling (PCASL) and gradient-echo/spin-echo (GESE) dynamic susceptibility contrast (DSC) MRI. Cerebral blood flow(CBF), cerebral blood volume, relative vessel size index (rVSI), and mean vessel density were calculated from modelfitting. Lower CBF from PCASL and SE DSC MRI was observed in the hippocampus of AD/MCI group. rVSI in thehippocampus of the AD/MCI group was larger than that of the two healthy groups (FDR-P ¼ 0.02). No difference in vesseldensity was detected between the groups. We also explored relationship of tau burden from 18F-flortaucipir positronemission tomography and vascular measures from MRI. Tau burden was associated with larger vessel size and lower CBFin the hippocampus. We postulate that larger vessel size may be associated with vascular alterations in AD/MCI.