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(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.

Institutional Animal Care and Use Committee. Results: Some extent of ARIA-E was observed in 20/28 APP+PS1, and 0/10 of the WT littermates. The most common pattern was observed in the ventral regions of the piriform cortical lobe and the medial nucleus of the amygdala. Histological results showed albumin in the parenchyma in the anatomical region that had an MR-visible ARIA-E lesion. ARIA-H was observed in 21/28 APP+PS1 mice, and in 0/10 of the WT littermates. These were primarily in the dorsal half of the cortex, but several appeared in the cerebellum. Perls’ iron positive foci histologically colocalized with these MR-visible ARIA-H lesions. Conclusions: In summary, we have demonstrated MR imaging can detect spontaneously-occurring intensity alterations consistent with ARIA-E and AREA-H in aged Ab-bearing transgenic mice, with the APP+PS1 strain appearing to be most sensitive. The pathogenesis of these findings and their relevance toMR clinical observations are being evaluated in ongoing studies with therapies targeting Ab reduction.