{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:18:40Z","timestamp":1791152320956,"version":"4.1.0"},"reference-count":60,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2013,10,15]]},"abstract":"<jats:p> Strong epidemiological and experimental evidence indicate that hypertension in the elderly predisposes to the development of Alzheimer's disease (AD), but the underlying mechanisms remain elusive. The present study was designed to characterize the additive\/synergistic effects of hypertension and aging on the expression of genes involved in \u03b2-amyloid generation and AD in the hippocampus, an area of brain contributing to higher cognitive function, which is significantly affected by AD both in humans and in mouse models of the disease. To achieve that goal, we induced hypertension in young (3 mo) and aged (24 mo) C57BL\/6 mice by chronic (4 wk) infusion of angiotensin II and assessed changes in hippocampal mRNA expression of genes involved in amyloid precursor protein (APP)-dependent signaling, APP cleavage, A\u03b2 processing and A\u03b2-degradation, synaptic function, dysregulation of microtubule-associated \u03c4 protein, and apolipoprotein-E signaling. Aged hypertensive mice exhibited spatial memory impairments in the Y-maze and impaired performance in the novel object recognition assay. Surprisingly, hypertension in aging did not increase the expression of APP, \u03b2- and \u03b3-secretases, or genes involved in tauopathy. These genes are all involved in the early onset form of AD. Yet, hypertension in aging was associated with changes in hippocampal expression of APP binding proteins, e.g., [Mint3\/amyloid \u03b2 A4 precursor protein-binding family A member 3 (APBA3), Fe65\/amyloid \u03b2 A4 precursor protein-binding family B member 1 (APBB1)], amyloid \u03b2 (A4) precursor-like protein 1 (APLP1), muscarinic M<jats:sub>1<\/jats:sub> receptor, and serum amyloid P component, all of which may have a role in the pathogenesis of late-onset AD. The hippocampal gene expression signature observed in aged hypertensive mice in the present study provides important clues for subsequent studies to elucidate the mechanisms by which hypertension may contribute to the pathogenesis and clinical manifestation of AD. <\/jats:p>","DOI":"10.1152\/ajpheart.00288.2013","type":"journal-article","created":{"date-parts":[[2013,8,17]],"date-time":"2013-08-17T04:02:21Z","timestamp":1376712141000},"page":"H1120-H1130","source":"Crossref","is-referenced-by-count":68,"title":["Synergistic effects of hypertension and aging on cognitive function and hippocampal expression of genes involved in \u03b2-amyloid generation and Alzheimer's disease"],"prefix":"10.1152","volume":"305","author":[{"given":"Anna","family":"Csiszar","sequence":"first","affiliation":[{"name":"Reynolds Oklahoma Center on Aging, Donald W. 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