期刊
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
卷 69, 期 11, 页码 1158-1167出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/NEN.0b013e3181fab558
关键词
Alzheimer; Capillary cerebral amyloid angiopathy; Cerebral amyloid angiopathy; Dementia; Dyshoric; Neuroinflammation
资金
- Internationale Stichting Alzheimer Onderzoek (ISAO) [07517, 09506]
- European Commission [LSHB-CT-2005-511977]
- Rijks Instituut voor Volksgezondheid en Milieu
Cerebral amyloid angiopathy (CAA) affects brain parenchymal and leptomeningeal arteries and arterioles but sometimes involves capillaries (capCAA) with spread of the amyloid into the surrounding neuropil, that is, dyshoric changes. We determined the relationship between capCAA and larger vessel CAA, A amyloid (AA) plaques, neurofibrillary changes, inflammation, and apolipoprotein E (APOE) in 22 cases of dyshoric capCAA using immunohistochemistry. The dyshoric changes contained predominantly AA1-40, whereas dense bulblike deposits adjacent to the capillary wall contained mostly AA1-42. There was an inverse local correlation between AA plaque load and capCAA severity (p = 0.01), suggesting that AA transport between the neuropil and the circulation may be mechanistically involved. Deposits of hyperphosphorylated tau and ubiquitin and clusters of activated microglia, resembling the changes around AA plaques, were found around capCAA but were absent around larger vessel CAA. In 14 cases for which APOE genotype was available, there was a high APOE-epsilon 4 allele frequency (54%; 43% homozygous). The severity of CapCAA increased with the number of epsilon 4-alleles; and APOE4 seemed to colocalize with capCAA by immunohistochemistry. These results suggest that capCAA is pathologically and possibly pathogenetically distinct from larger vessel CAA, and that it is associated with a high APOE-epsilon 4 allele frequency.
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