The DOI matches its Crossref record; 65 of the 66 references it cites were found in a registry or an index.
Amyloid Angiopathy and Variability in Amyloid β Deposition Is Determined by Mutation Position in Presenilin-1-Linked Alzheimer’s Disease
Open accessAbstract
The presenilins (PSs) are components of large molecular complexes that contain beta-catenin and function as gamma-secretase. We report here a striking correlation between amyloid angiopathy and the location of mutation in PS-1 linked Alzheimer's disease. The amount of amyloid beta protein, Abeta(42(43)), but not Abeta(40,) deposited in the frontal cortex of the brain is increased in 54 cases of early-onset familial Alzheimer's disease, encompassing 25 mutations in the presenilin-1 (PS-1) gene, compared to sporadic Alzheimer's disease. The amount of Abeta(40) in PS-1 Alzheimer's disease varied according to the copy number of epsilon4 alleles of the Apolipoprotein E gene. Although the amounts of Abeta(40) and Abeta(42(43)) deposited did not correlate with the genetic location of the mutation in a strict linear sense, the histological profile did so vary. Cases with mutations between codon 1 and 200 showed, in frontal cortex, many diffuse plaques, few cored plaques, and mild or moderate amyloid angiopathy. Cases with mutations occurring after codon 200 also showed many diffuse plaques, but the number and size of cored plaques were increased (even when epsilon4 allele was not present) and these were often clustered around blood vessels severely affected by amyloid angiopathy. Similarly, diverging histological profiles, mainly according to the degree of amyloid angiopathy, were seen in the cerebellum. Mutations in the PS-1 gene may therefore alter the topology of the PS-1 protein so as to favor Abeta formation and deposition, generally, but also to facilitate amyloid angiopathy particularly in cases in which the mutation lies beyond codon 200. Finally we report that the amount of Abeta(42(43)) deposited in the brain correlated with the amount of this produced in culture by cells bearing the equivalent mutations.
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“Several PSEN1 mutations are associated with AD and correlates with pathological CAA severity [610].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [610]
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Self-citationIncreased amyloid-β42(43) in brains of mice expressing mutant presenilin 1
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Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994
Network abnormalities and interneuron dysfunction in Alzheimer disease
Palop, J. J., & Mucke, L. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.141 · Cited by 1,022
Cerebral amyloid angiopathy and Alzheimer disease — one peptide, two pathways
Greenberg, S. M., Bacskai, B. J., Hernandez-Guillamon, M., Pruzin, J., Sperling, R., & van Veluw, S. J. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-019-0281-2 · Cited by 947
Alzheimer’s disease: A matter of blood–brain barrier dysfunction?
Montagne, A., Zhao, Z., & Zlokovic, B. V. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20171406 · Cited by 672
Bateman, R. J., Aisen, P. S., De Strooper, B., Fox, N. C., Lemere, C. A., Ringman, J. M., Salloway, S., Sperling, R. A., Windisch, M., & Xiong, C. (2010) · Alzheimer's Research & Therapy · doi:10.1186/alzrt59 · Cited by 573
Metadata
- Authors
- Mann, D. M. A., Pickering-Brown, S. M., Takeuchi, A., & Iwatsubo, T.
- Affiliations
- University of Manchester (GB)
- The University of Tokyo (JP)
- Corresponding author
- Mann, David M.A.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2001-06
- Volume
- 158
- Issue
- 6
- Pages
- 2165-2175
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1891993
- OpenAlex
- W1965252410
- Cited by
- 182
- References
- 66
- Citations by year
- 2025: 2 · 2024: 13 · 2023: 7 · 2022: 11 · 2021: 10 · 2020: 5 · 2019: 6 · 2018: 7 · 2017: 4 · 2016: 7 · 2015: 12 · 2014: 2 · 2013: 8 · 2012: 6
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Clinical Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- amyloid angiopathy, presenilin 1, Alzheimer's disease, amyloid-beta deposition, amyloid-beta 42, Aβ40, familial Alzheimer's disease, mutation position, APOE ε4, cerebral amyloid angiopathy, diffuse plaques, frontal cortex, cerebellum, gamma-secretase, protein topology
- MeSH terms
- Adult, Alzheimer Disease, Animals, Apolipoproteins E, Cerebellum, Female, Frontal Lobe, Genotype, Humans, Male, Membrane Proteins, Middle Aged, Mutation, Peptide Fragments, Genetic Variation, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, COS Cells, Presenilin-1
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