beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease.
Open accessAbstract
Reinvestigation of the chemical structure of beta-amyloid peptide (A beta) deposits in the vascular tissue of Alzheimer disease brains revealed that the 42-residue form A beta-(1-42), rather than the more soluble A beta-(1-40) form, is the predominant peptide. Following removal of the surrounding tissue with SDS and collagenase, A beta was solubilized in formic acid and purified by Superose 12 chromatography. Peptides generated by enzymatic and chemical digestion of the A beta were purified by HPLC and characterized by amino acid analysis, sequence analysis, and mass spectrometry. In the leptomeningeal vessels, the average ratio of A beta-(1-42)/A beta-(1-40) was 58:42, whereas in the parenchymal vessels this ratio was 75:25. Interestingly, vascular A beta contains considerably less isomerized and racemized aspartyl residues than does neuritic plaque A beta, suggesting that the vascular amyloid is "younger." The discrete nature of the bands and spherical deposits of A beta associated with arterioles and capillaries, respectively, suggests that this amyloid arises from the vascular tissue itself. Increasing A beta deposition appears to lead to the distortion and occlusion of capillaries, which may contribute significantly to the pathology of Alzheimer disease.
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- Authors
- Roher, A. E., Lowenson, J. D., Clarke, S., Woods, A. S., Cotter, R. J., Gowing, E., & Ball, M. J.
- Affiliations
- Wayne State University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1993-11-15
- Volume
- 90
- Issue
- 22
- Pages
- 10836-10840
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC47873
- OpenAlex
- W2081182167
- Cited by
- 740
- References
- 19
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 26 · 2023: 14 · 2022: 45 · 2021: 20 · 2020: 23 · 2019: 21 · 2018: 23 · 2017: 20 · 2016: 24 · 2015: 28 · 2014: 24 · 2013: 28 · 2012: 17
- FWCI
- 16.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- American Health Assistance Foundation
- American Heart Association
- National Institutes of Health (AG‐08017)
- National Institute on Aging (P30AG008017)
- National Institute of General Medical Sciences (GM 26020)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- amyloid-beta, Alzheimer disease pathology, leptomeningeal vessels, arterioles, capillaries, capillary occlusion
- MeSH terms
- Alzheimer Disease, Amino Acid Sequence, Blood-Brain Barrier, Brain Chemistry, Cerebrovascular Circulation, Humans, Microscopy, Fluorescence, Molecular Sequence Data, Oligopeptides, Mass Spectrometry, Amyloid beta-Peptides
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