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Cited by 69

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Synergistic effects of hypertension and aging on cognitive function and hippocampal expression of genes involved in β-amyloid generation and Alzheimer's disease

Csiszar, Anna, Tucsek, Zsuzsanna, Toth, Peter, Sosnowska, Danuta, Gautam, Tripti, Koller, Akos, Deak, Ferenc, Sonntag, William E., Ungvari, Zoltan·2013·American Journal of Physiology-Heart and Circulatory Physiology
DOI 10.1152/ajpheart.00288.2013
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Abstract

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 β-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, Aβ processing and Aβ-degradation, synaptic function, dysregulation of microtubule-associated τ 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, β- and γ-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 β A4 precursor protein-binding family A member 3 (APBA3), Fe65/amyloid β A4 precursor protein-binding family B member 1 (APBB1)], amyloid β (A4) precursor-like protein 1 (APLP1), muscarinic M 1 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.

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Metadata

Authors
Csiszar, A., Tucsek, Z., Toth, P., Sosnowska, D., Gautam, T., Koller, A., Deak, F., Sonntag, W. E., & Ungvari, Z.
Affiliations
  • Reynolds Oklahoma Center on Aging, Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma;
  • Department of Pathophysiology and Gerontology, Medical School and Szentágothai Research Centre, University of Pecs, Pecs, Hungary; and
Venue
American Journal of Physiology-Heart and Circulatory Physiology
Publisher
American Physiological Society
Published
2013-10-15
Volume
305
Issue
8
Pages
H1120-H1130
ISSN
  • 0363-6135
  • 1522-1539
DOI
10.1152/ajpheart.00288.2013
Cited by
69
References
13
Language
en

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CoChat. (2026). Citation check: Synergistic effects of hypertension and aging on cognitive function and hippocampal expression of genes involved in β-amyloid generation and Alzheimer's disease. https://app.cochat.ai/papers/10.1152/ajpheart.00288.2013
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Csiszar, A., Tucsek, Z., Toth, P., Sosnowska, D., Gautam, T., Koller, A., Deak, F., Sonntag, W. E., & Ungvari, Z. (2013). Synergistic effects of hypertension and aging on cognitive function and hippocampal expression of genes involved in β-amyloid generation and Alzheimer's disease. American Journal of Physiology-Heart and Circulatory Physiology. https://doi.org/10.1152/ajpheart.00288.2013

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