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.

临床研究表明，与阿尔茨海默病（AD）和动脉高血压相关的脑淀粉样血管病（CAA）是脑微出血（CMHs）的独立危险因素。为了检验淀粉样蛋白病理学和高血压相互作用以促进 CMHs 发展的假设，我们通过血管紧张素 II (Ang II) 和 NO 合成抑制剂 L-NAME 治疗在 AD 的 Tg2576 小鼠模型和各自的对照中诱导高血压。比较了 CMH 的数量、大小、定位和神经学后果（步态改变）。我们发现，与对照小鼠相比，在 TG2576 小鼠中，相同水平的高血压导致 CMH 负担显着增加和 CMH 相关步态改变的恶化。在高血压 TG2576 小鼠中，CMHs 主要位于皮质-皮质下边界的大脑皮层，模仿 CAA 患者的临床表现。总的来说，淀粉样蛋白病理加剧了高血压的影响，促进了 CMHs 的发生，这可能导致它们对认知功能产生有害影响。预防 CMHs 的治疗策略可降低血压并保持微血管完整性，有望对高危老年 AD 患者发挥神经保护作用。