Kim, Min-Soo Bang, Jihye Kim, Bu-Yeo Jeon, Won Kyung 2024-01-19T14:04:02Z 2024-01-19T14:04:02Z 2022-01-25 2021-07 1079-5006 https://pubs.kist.re.kr/handle/201004/116699 Cerebrovascular lesions are widely prevalent in patients with Alzheimer's disease (AD), but their relationship to the pathophysiology of AD remains poorly understood. An improved understanding of the interaction of cerebrovascular damage with AD is crucial for the development of therapeutic approaches. Herein, we investigated the effects of chronic cerebral hypoperfusion (CCH) in a 5XFAD transgenic (Tg) mouse model of AD. We established CCH conditions in both Tg and non-Tg mice by inducing unilateral common carotid artery occlusion (UCCAO). Cognitive performance in mice was evaluated, and their brain tissue was examined for amyloid-beta (A beta) pathology to elucidate possible mechanisms. We found that UCCAO-operated Tg mice showed impaired cognitive flexibility in the reversal phase of the hidden-platform water maze task compared to sham-operated Tg mice. Interestingly, UCCAO-operated Tg mice used fewer spatial cognitive strategies than sham-operated Tg mice during reversal learning. These cognitive deficits were accompanied by increased A beta plaque burden and A beta 42 levels in the hippocampus and prefrontal cortex, 2 regions that play essential roles in the regulation of cognitive flexibility. Furthermore, changes in cognitive flexibility are strongly correlated with the expression levels of enzymes related to A beta clearance, such as neprilysin and insulin-degrading enzymes. These findings suggest that, in 5XFAD mice, impaired cognitive flexibility is related to CCH, and that A beta clearance might be involved in this process. English Gerontological Society of America Impaired Cognitive Flexibility Induced by Chronic Cerebral Hypoperfusion in the 5XFAD Transgenic Mouse Model of Mixed Dementia Article 10.1093/gerona/glab075 1 Journals of Gerontology - Series A Biological Sciences and Medical Sciences, v.76, no.7, pp.1169 - 1178 Journals of Gerontology - Series A Biological Sciences and Medical Sciences 76 7 1169 1178 Y scie ssci scopus 000672804600004 2-s2.0-85108303054 Geriatrics & Gerontology Gerontology Geriatrics & Gerontology Article ALZHEIMERS-DISEASE BLOOD-FLOW DYSFUNCTION MEMORY NEPRILYSIN EXPRESSION PATHOLOGY RAT KEY Unilateral common carotid artery occlusion Alzheimer&apos s disease Amyloid-beta Reversal learning