RELATIONSHIP BETWEEN CEREBRAL BLOOD FLOW AND CORTICAL LAYER I ASTROCYTES IN A TRANSGENIC MOUSE MODEL OF ALZHEIMER'S DISEASE

Abstract

(WT) mice (n1⁄48) were studied at 17-19 months-of-age. Whole brain perfusion images (360 mm isotropic spatial resolution) were acquired with a multi-slice, pseudocontinuous ASL pulse sequence on a 7T animal MRI system. Mice were scanned both in the awake state and under sevoflurane anesthesia (a known vasodilator) to assess group differences in resting CBF and vasodilatory response, respectively. The perfusion images were co-registered to anatomical MR images acquired during the same session, and spatially normalized to reference coordinate space to generate regional perfusion measures using a fully-automated image processing pipeline (NIGHTWING TM, Biospective Inc.). Results: The Tg mice exhibited a lower resting CBF (w15%) compared to theWTmice in most brain regions. Under sevoflurane, this difference increased tow30% as the Tgmice exhibited an attenuated vasodilatory response relative to the WT group. The coefficient of variation was higher in the awake mice. Conclusions: This study demonstrated that APPoverexpressing Tg mice have impaired resting cerebrovascular function, which is exacerbated under a challenge condition. The greater effect size of the challenge state suggests that utilization of an appropriate vasodilatory challenge could be a useful paradigm in human AD studies.