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In this study, we aimed to assess cerebral blood flow (CBF) and cerebrovascular response (CVR) as early, pre\u2010symptomatic (3\u00a0months of age), imaging markers in a bigenic model of Alzheimer's disease (APP.V717IxTau.P301L, biAT) and in the monogenic parental strains. We further developed our previously published combination of pulsed arterial spin labeling perfusion MRI and hypo\u2010ventilation paradigm, which allows weaning of the mice from the ventilator. Furthermore, the commonly used isoflurane anesthesia induces vasodilation and is thereby inherently a vascular challenge. We therefore assessed perfusion differences in the mouse models under free\u2010breathing isoflurane conditions. We report (i) that we can determine CBF and hypoventilation\u2010based CVR under ketamine\/midazolam anesthesia and wean mice from the ventilator, making it a valuable tool for assessment of CBF and CVR in mice, (ii) that biAT mice exhibit lower cortical CBF than wild\u2010type mice at age 3\u00a0months<jats:italic>,<\/jats:italic> (iii) that CVR was increased in both biAT and APP.V717I mice but not in Tau.P301L mice, identifying the APP genotype as a strong influencer of brain CVR and (iv) that perfusion differences at baseline are masked by the widely used isoflurane anesthesia.<\/jats:p>","DOI":"10.1002\/nbm.4037","type":"journal-article","created":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T11:14:15Z","timestamp":1543490055000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Longitudinal assessment of cerebral perfusion and vascular response to hypoventilation in a bigenic mouse model of Alzheimer's 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