Amino- and carboxyl-terminal heterogeneity of β-amyloid peptides deposited in human brain
Abstract
We aimed to determine quantitatively the fine amino- and carboxyl-terminal structure of A beta peptides deposited in human brain using a set of 12 anti-A beta antibodies that distinguish between terminal modifications including isomerization, stereoisomerization, limited proteolysis, and cyclization. Immunochemical examination of cortical blocks from aged subjects distinguished by their total plaque load and from a young Down's syndrome patient identified the major invariantly deposited species as A beta x-42 (X = 1(D-aspartate) and 3(pyroglutamate) and/or 11(pyroglutamate)). These molecular forms, presumably representing by-products of metabolic intermediates toward degradation, are similar in being resistant to major aminopeptidases. A beta 17-42 ("p3' fragment), a major secreted form of truncated A beta with high insolubility, was found to be a minor one. A possible interpretation for these observations would be that proteolysis of A beta from its amino terminus may limit the rate of A beta catabolism.
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N-terminally modified or truncated forms of Aβ, which predominate in AD brain, are minor species in Tg2576 brain that only begin to appear in very old mice.
“Thus, it appears that N-terminally modified or truncated forms of A, which predominate in AD brain (Saido et al., 1995(Saido et al., , 1996;;Hosoda et al., 1998), are minor species in Tg2576 brain that only begin to appear in very old mice.”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Saido et al., 1996
Much of the Aβ in AD brain is N-terminally truncated or modified.
“Much of the A in AD brain is N-terminally truncated or modified (Saido et al., 1995(Saido et al., , 1996;;Hosoda et al., 1998)”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Saido et al., 1996
N-terminally truncated or modified Aβ [especially forms beginning with pyroglutamate at position 3 (3pE)] and oligomers are resistant to proteolysis.
“Because N-terminally truncated or modified A [especially forms beginning with pyroglutamate at position 3 (3pE)] and oligomers are resistant to proteolysis (Saido et al., 1996;Kuo et al., 1998)”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Saido et al., 1996
These modifications of Aβ are thought to be important for amyloid deposition.
“these modifications of A are thought to be important for amyloid deposition.”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Saido et al., 1996
N-terminal Aβ1-x/βCTF-specific antibodies fail to label N-truncated Aβ42 peptides that appear to be particularly important in AD.
“N-terminal Aβ1-x/βCTF-specific antibodies also fail to label N-truncated Aβ42 peptides that appear to be particularly important in AD [60, 98, 157, 158, 206].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [157]
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- Authors
- Saido, T. C., Yamao-Harigaya, W., Iwatsubo, T., & Kawashima, S.
- Affiliations
- Tokyo Metropolitan Institute of Medical Science (JP)
- The University of Tokyo (JP)
- Corresponding author
- Saido, Takaomi C.
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 1996-09
- Volume
- 215
- Issue
- 3
- Pages
- 173-176
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2012288880
- Cited by
- 270
- References
- 11
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 11 · 2023: 11 · 2022: 4 · 2021: 7 · 2020: 14 · 2019: 6 · 2018: 6 · 2017: 14 · 2016: 4 · 2015: 9 · 2014: 14 · 2013: 15 · 2012: 8
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Uehara Memorial Foundation
- Ministry of Education, Culture, Sports, Science and Technology
- Naito Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta, amyloid plaques, terminal modification, pyroglutamic acid, D-aspartate, anti-amyloid antibodies, Down syndrome, proteolysis, human brain
- MeSH terms
- Adult, Alzheimer Disease, Brain, Humans, Blotting, Western, Amyloid beta-Protein Precursor
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