A distinct brain beta amyloid signature in cerebral amyloid angiopathy compared to Alzheimer's disease
A distinct brain beta amyloid signature in cerebral amyloid angiopathy compared to Alzheimer's disease
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DOI：
10.1016/j.neulet.2019.02.033
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发表时间：
2019-05-14
影响因子：
2.5
通讯作者：
Brinkmalm, Gunnar
中科院分区：
文献类型：
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作者：
Gkanatsiou, Eleni;Portelius, Erik;Brinkmalm, Gunnar
脑淀粉样血管病（CAA）是一种存在于超过50%的痴呆老年人和超过80%的阿尔茨海默病（AD）患者中的血管疾病。CAA和AD两者的特征在于细胞外A β沉积，区别在于CAA具有血管沉积，而AD具有淀粉样斑块。在这项研究中，我们使用免疫沉淀（IP）结合质谱（MS）来检验以下假设：A β肽模式在仅患有所有斑块病理学的受试者与患有A β斑块病理学和CAA病理学的受试者之间不同。使用70%甲酸提取来自12个AD脑的枕叶，范围从无CAA到严重CAA，随后进行IP-MS分析。与CAA受试者相比，无CAA受试者的A β肽模式差异很大。在CAA病例中，最丰富的A β肽终止于氨基酸40，包括A β 1-40（P = .048）和A β 2-40（P = .0253），与无CAA病例相比显著增加。这与没有CAA的受试者形成对比，在没有CAA的受试者中，最丰富的A β肽在氨基酸42处结束，其中A β 1-42（P = .0101）和A β 2-42（P = .0051）以及焦谷氨酸（pGlu）修饰的肽pGlu A β 3-42（P = 0.0177）和pGlu A β 11-42（P = 0.0088）与CAA受试者相比显著增加。结果与早期的免疫组织化学数据一致，并表明血管中发现的A β沉积物的分子组成与实质沉积物不同，表明它们来自不同的致病途径。这些信息可能有助于开发病理学特异性生物标志物。
Cerebral amyloid angiopathy (CAA) is a type of vascular disease present in more than 50% of demented elderly and more than 80% of Alzheimer's disease (AD) patients. Both CAA and AD are characterized by extracellular A beta deposits with the distinction that CAA has vascular deposits while AD has amyloid plaques. In this study, we used immunoprecipitation (IP) in combination with mass spectrometry (MS) to test the hypothesis that the A beta peptide pattern differs between subjects having All plaque pathology only and subjects with A beta plaque pathology together with CAA pathology. Occipital lobes from 12 AD brains, ranging from no CAA to severe CAA, were extracted using 70% formic acid followed by IP-MS analysis. The A beta peptide pattern differed greatly between subjects with no CAA compared to subjects with CAA. In cases with CAA, the most abundant A beta peptides ended at amino acid 40 including A beta 1-40 (P = .048) and A beta 2-40 (P = .0253) which were significantly increased compared to cases with no CAA. This was in contrast to subjects with no CAA where the most abundant A beta peptides ended at amino acid 42 of which A beta 1-42 (P = .0101) and A beta 2-42 (P = .0051) as well as the pyroglutamate (pGlu)-modified peptides pGlu A beta 3-42 (P = .0177), and pGlu A beta 11-42 (P = .0088) were significantly increased compared to CAA subjects. The results are in line with earlier immunohistochemistry data and show that the molecular composition of the A beta deposits found in blood vessels are different to the parenchymal deposits, suggesting they arise from distinct pathogenic pathways. This information may be useful in the development of pathology-specific biomarkers.