期刊
GEROSCIENCE
卷 42, 期 6, 页码 1685-1698出版社
SPRINGER
DOI: 10.1007/s11357-020-00256-3
关键词
Dementia; Microbleed; Arteriole; Gait dysfunction; Cerebral amyloid angiopathy
资金
- American Heart Association
- Oklahoma Center for the Advancement of Science and Technology
- National Institute on Aging [R01-AG047879, R01-AG038747, R01-AG055395]
- National Institute of Neurological Disorders and Stroke (NINDS) [R01-NS056218, R01-NS100782]
- National Institute of General Medical Sciences Oklahoma Shared Clinical and Translational Resources (OSCTR) [GM104938]
- Presbyterian Health Foundation
- NIA [T32AG052363]
- Oklahoma Nathan Shock Center [P30AG050911]
- Cellular and Molecular GeroScience CoBRE [1P20GM125528, 5337]
Clinical studies show that cerebral amyloid angiopathy (CAA) associated with Alzheimer's disease (AD) and arterial hypertension are independent risk factors for cerebral microhemorrhages (CMHs). To test the hypothesis that amyloid pathology and hypertension interact to promote the development of CMHs, we induced hypertension in the Tg2576 mouse model of AD and respective controls by treatment with angiotensin II (Ang II) and the NO synthesis inhibitor L-NAME. The number, size, localization, and neurological consequences (gait alterations) of CMHs were compared. We found that compared to control mice, in TG2576 mice, the same level of hypertension led to significantly increased CMH burden and exacerbation of CMH-related gait alterations. In hypertensive TG2576 mice, CMHs were predominantly located in the cerebral cortex at the cortical-subcortical boundary, mimicking the clinical picture seen in patients with CAA. Collectively, amyloid pathologies exacerbate the effects of hypertension, promoting the genesis of CMHs, which likely contribute to their deleterious effects on cognitive function. Therapeutic strategies for prevention of CMHs that reduce blood pressure and preserve microvascular integrity are expected to exert neuroprotective effects in high-risk elderly AD patients.
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