期刊
ACTA NEUROPATHOLOGICA
卷 135, 期 5, 页码 681-694出版社
SPRINGER
DOI: 10.1007/s00401-018-1834-y
关键词
Microinfarct; Hippocampus; Cerebral amyloid angiopathy; Cognitive decline; Alzheimer; Dementia
资金
- Alzheimer Forschung Initiative (AFI) [13803]
- Fonds Wetenschappelijk Onderzoek Vlaanderen [FWO- G0F8516 N]
- Vlaamse Impulsfinanciering voor Netwerken voor Dementieonderzoek [IWT 135043]
- German Federal Ministry of Education and Research [FTLDc O1GI1007A]
- EU [FAIR-PARKII 633190]
- foundation of the state Baden-Wurttemberg [D.3830]
- Thierry Latran Foundation
- ALS Association
- BIU
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.
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