The Expression of Activin Receptor-Like Kinase 1 (ACVRL1/ALK1) in Hippocampal Arterioles Declines During Progression of Alzheimer's Disease.
The Expression of Activin Receptor-Like Kinase 1 (ACVRL1/ALK1) in Hippocampal Arterioles Declines During Progression of Alzheimer's Disease.
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在阿尔茨海默病的进展过程中，海马小动脉中激活素受体样激酶 1 (ACVRL1/ALK1) 的表达下降。
DOI：
10.1093/texcom/tgaa031
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发表时间：
2020
影响因子：
--
通讯作者：
Delalle,Ivana
中科院分区：
文献类型：
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作者：
Anderson,KelleyE;Bellio,ThomasA;Aniskovich,Emily;Adams,StephanieL;Blusztajn,JanKrzysztof;Delalle,Ivana
阿尔茨海默病(AD)中的脑淀粉样血管病(AD)是脑血管壁中β淀粉样蛋白(Aβ)的沉积，通常伴随着β在脑实质中的积聚，并导致血管结构和功能的异常。我们最近发现，在AD的晚期，CA3锥体神经元中BMP9/BMP10(骨形态发生蛋白)信号蛋白的I型受体激活素受体样激酶1(ALK1)的免疫反应性降低。在此，我们用免疫组织化学方法研究了阿尔茨海默病患者死后海马区ALK1的血管表达情况。AD患者(Braak和Braak IV和V期[BBIV-V]；临床痴呆分级[CDR1-2])的海马区小动脉壁ALK1信号强度较早期AD病理改变但认知功能完整或轻度认知损害的受试者(BBIII；CDR0-0.5)低35%。在所有分析病例中，小动脉壁Aβ信号强度相似。这些数据表明，正如先前在特定神经元群体中所证明的那样，ALK1在血管中的表达也容易受到AD病理生理过程的影响，可能与CAA有关。然而，皮质小动脉可能仍然对ALK1配体有反应，如BMP9和BMP10，在早期和中期AD。
Cerebral amyloid angiopathy (CAA) in Alzheimer’s disease (AD)—deposition of beta amyloid (Aβ) within the walls of cerebral blood vessels—typically accompanies Aβ buildup in brain parenchyma and causes abnormalities in vessel structure and function. We recently demonstrated that the immunoreactivity of activin receptor-like kinase 1 (ALK1), the type I receptor for circulating BMP9/BMP10 (bone morphogenetic protein) signaling proteins, is reduced in advanced, but not early stages of AD in CA3 pyramidal neurons. Here we characterize vascular expression of ALK1 in the context of progressive AD pathology accompanied by amyloid angiopathy in postmortem hippocampi using immunohistochemical methods. Hippocampal arteriolar wall ALK1 signal intensity was 35% lower in AD patients (Braak and Braak Stages IV and V [BBIV-V]; clinical dementia rating [CDR1-2]) as compared with subjects with early AD pathologic changes but either cognitively intact or with minimal cognitive impairment (BBIII; CDR0-0.5). The intensity of Aβ signal in arteriolar walls was similar in all analyzed cases. These data suggest that, as demonstrated previously for specific neuronal populations, ALK1 expression in blood vessels is also vulnerable to the AD pathophysiologic process, perhaps related to CAA. However, cortical arterioles may remain responsive to the ALK1 ligands, such as BMP9 and BMP10 in early and moderate AD.