Capillary cerebral amyloid angiopathy in Alzheimer's disease: association with allocortical/hippocampal microinfarcts and cognitive decline
Capillary cerebral amyloid angiopathy in Alzheimer's disease: association with allocortical/hippocampal microinfarcts and cognitive decline
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DOI：
10.1007/s00401-018-1834-y
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发表时间：
2018-05-01
影响因子：
12.7
通讯作者：
Thal, Dietmar Rudolf
中科院分区：
文献类型：
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作者：
Hecht, Moritz;Kraemer, Lara Maria;Thal, Dietmar Rudolf
脑淀粉样血管病(CAA)是由淀粉样β蛋白(Aβ)沉积在大脑和软脑膜血管壁中引起的，与阿尔茨海默病(AD)有关。毛细血管Aβ沉积见于部分CAA病例，代表一种独特的CAA类型，称为毛细血管CAA或CAA 1型。这种类型的CAA与载脂蛋白E epsilon 4等位基因的存在密切相关。与CAA 1型相关的AD患者通常表现出更严重的Aβ斑块病理，但不太广泛的神经原纤维缠结(NFT)病理。本研究的目的是分析毛细血管CAA及其对脑血流的影响是否对痴呆有影响。为了达到这个目的，我们对284例痴呆和非痴呆患者的尸检病例进行了神经病理学评估。我们评估了CAA及其亚型的存在，以及出血和梗塞的存在。毛细血管CAA和CAA严重程度与构成海马区CA1区的异地皮质微梗塞有关。因此，异位皮质微梗塞、毛细血管CAA和CAA严重程度与认知功能下降有关。总而言之，皮质微梗塞、CAA严重程度和CAA的毛细血管类型相互关联，并与认知功能减退的发展有关。因此，患有1型CAA(毛细血管CAA)的AD患者似乎不仅由于AD相关的Aβ斑块和NFT病理，而且由于与CAA 1型和CAA严重程度相关的海马区微梗塞而出现痴呆症状，这损害了对记忆功能重要的大脑区域。
Cerebral amyloid angiopathy (CAA) is caused by the deposition of the amyloid beta-protein (A beta) in the wall of cerebral and leptomeningeal blood vessels and is related to Alzheimer's disease (AD). Capillary A beta deposition is observed in a subset of CAA cases and represents a distinct type of CAA named capillary CAA or CAA type 1. This type of CAA is strongly associated with the presence of the apolipoprotein E epsilon 4 allele. CAA type 1-associated AD cases often exhibit a more severe A beta plaque pathology but less widespread neurofibrillary tangle (NFT) pathology. The objective of this study was to analyze whether capillary CAA and its effects on cerebral blood flow have an impact on dementia. To address this objective, we performed neuropathological evaluation of 284 autopsy cases of demented and non-demented individuals. We assessed the presence of CAA and its subtypes as well as for that of hemorrhages and infarcts. Capillary CAA and CAA severity were associated with allocortical microinfarcts, comprising the CA1 region of the hippocampus. Allocortical microinfarcts, capillary CAA and CAA severity were, thereby, associated with cognitive decline. In conclusion, allocortical microinfarcts, CAA severity, and the capillary type of CAA were associated with one another and with the development of cognitive decline. Thus, AD cases with CAA type 1 (capillary CAA) appear to develop dementia symptoms not only due to AD-related A beta plaque and NFT pathology but also due to hippocampal microinfarcts that are associated with CAA type 1 and CAA severity, and that damage a brain region important for memory function.