The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Disruption of Arterial Perivascular Drainage of Amyloid-β from the Brains of Mice Expressing the Human APOE ε4 Allele
Open accessAbstract
Failure of elimination of amyloid-β (Aβ) from the brain and vasculature appears to be a key factor in the etiology of sporadic Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). In addition to age, possession of an apolipoprotein E (APOE) ε4 allele is a strong risk factor for the development of sporadic AD. The present study tested the hypothesis that possession of the APOE ε4 allele is associated with disruption of perivascular drainage of Aβ from the brain and with changes in cerebrovascular basement membrane protein levels. Targeted replacement (TR) mice expressing the human APOE3 (TRE3) or APOE4 (TRE4) genes and wildtype mice received intracerebral injections of human Aβ(40). Aβ(40) aggregated in peri-arterial drainage pathways in TRE4 mice, but not in TRE3 or wildtype mice. The number of Aβ deposits was significantly higher in the hippocampi of TRE4 mice than in the TRE3 mice, at both 3- and 16-months of age, suggesting that clearance of Aβ was disrupted in the brains of TRE4 mice. Immunocytochemical and Western blot analysis of vascular basement membrane proteins demonstrated significantly raised levels of collagen IV in 3-month-old TRE4 mice compared with TRE3 and wild type mice. In 16-month-old mice, collagen IV and laminin levels were unchanged between wild type and TRE3 mice, but were lower in TRE4 mice. The results of this study suggest that APOE4 may increase the risk for AD through disruption and impedance of perivascular drainage of soluble Aβ from the brain. This effect may be mediated, in part, by changes in age-related expression of basement membrane proteins in the cerebral vasculature.
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Cites
Decreased Clearance of CNS β-Amyloid in Alzheimer’s Disease
Mawuenyega, K. G., Sigurdson, W., Ovod, V., Munsell, L., Kasten, T., Morris, J. C., Yarasheski, K. E., & Bateman, R. J. (2010) · Science · doi:10.1126/science.1197623 · Cited by 2,078
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Self-citationApoE-4 and Age at Onset of Alzheimer's Disease: The NIMH Genetics Initiative
Blacker, D., Haines, J. L., Rodes, L., Terwedow, H., Go, R. C. P., Harrell, L. E., Perry, R. T., Bassett, S. S., Chase, G., Meyers, D., et al. (1997) · Neurology · doi:10.1212/wnl.48.1.139 · Cited by 479
Microglia Mediate the Clearance of Soluble Aβ through Fluid Phase Macropinocytosis
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Self-citationCerebral amyloid angiopathy and cognitive function: The HAAS autopsy study
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Self-citationApolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C., & Bu, G. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0228-7 · Cited by 1,425
The overlap between vascular disease and Alzheimer’s disease - lessons from pathology
Attems, J., & Jellinger, K. A. (2014) · BMC Medicine · doi:10.1186/s12916-014-0206-2 · Cited by 739
Mechanisms of fluid movement into, through and out of the brain: evaluation of the evidence
Hladky, S. B., & Barrand, M. A. (2014) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-11-26 · Cited by 633
The vascular basement membrane in the healthy and pathological brain
Thomsen, M. S., Routhe, L. J., & Moos, T. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17722436 · Cited by 490
Metadata
- Authors
- Hawkes, C. A., Sullivan, P. M., Hands, S., Weller, R. O., Nicoll, J. A. R., & Carare, R. O.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-07-25
- Volume
- 7
- Issue
- 7
- Pages
- e41636
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2053005839
- Cited by
- 180
- References
- 19
- FWCI
- 9.43
- Type
- journal article
- Language
- en
- Open access
- gold
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- Hawkes, C. A., Sullivan, P. M., Hands, S., Weller, R. O., Nicoll, J. A. R., & Carare, R. O. (2012). Disruption of Arterial Perivascular Drainage of Amyloid-β from the Brains of Mice Expressing the Human APOE ε4 Allele. PLoS ONE. https://doi.org/10.1371/journal.pone.0041636
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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