{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:40:11Z","timestamp":1788309611970,"version":"build-2803163510"},"reference-count":46,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2020,3,10]]},"abstract":"<jats:p>The blood-brain barrier (BBB) can restrict the therapeutic effects of Alzheimer\u2019s disease (AD) medications. While a large number of AD drug treatment trials targeting BBB dynamics have emerged, most have failed due to insufficient permeability. Furthermore, a subset of AD cases, which also feature chronic hypoperfusion are complicated by BBB deficits. We used a mouse model of AD with chronic hypoperfusion\u2014transgenic mice (PS1V97L) with right common carotid artery ligation. In this model, we assessed how chronic cerebral hypoperfusion changed the pathophysiological processes that increase BBB permeability. Compared with control mice, AD mice with chronic hypoperfusion revealed significantly upregulated expression of the receptor for advanced glycation end products (RAGE) on the BBB. Upregulated RAGE caused increased accumulation of amyloid-\u03b2 (A\u03b2) in the brain in these mice. Upregulation of RAGE (or binding to A\u03b2) can promote activation of the NF-\u03baB pathway and enhance oxidative stress and increase the release of pro-inflammatory factors. These factors promoted the reduction of tight junction proteins between the endothelial cells in the BBB and increased its permeability. These findings suggest that the transporter RAGE dysregulation on the BBB initiates a series of pathophysiological processes which lead to increased BBB permeability. Taken together, we have shown that chronic hypoperfusion can serve to enhance and aggravate the BBB impairment in AD.<\/jats:p>","DOI":"10.3233\/jad-191045","type":"journal-article","created":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T16:33:53Z","timestamp":1580229233000},"page":"261-275","source":"Crossref","is-referenced-by-count":22,"title":["The Effect of Chronic Cerebral Hypoperfusion on Blood-Brain Barrier Permeability in a Transgenic Alzheimer\u2019s Disease Mouse Model (PS1V97L)1"],"prefix":"10.1177","volume":"74","author":[{"given":"Heyun","family":"Yang","sequence":"first","affiliation":[{"name":"Innovation Center for Neurological Disorders, Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China"},{"name":"Department of Neurology, The First Hospital of Kunming, Kunming, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Innovation Center for 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