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Amino- and carboxyl-terminal heterogeneity of β-amyloid peptides deposited in human brain

Saido, Takaomi C., Yamao-Harigaya, Wakako, Iwatsubo, Takeshi, Kawashima, Seiichi·1996·Neuroscience Letters

DOI 10.1016/0304-3940(96)12970-0

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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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Background
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Dipeptidyl-Peptidase Activity of Meprin β Links N-truncation of Aβ with Glutaminyl Cyclase-Catalyzed pGlu-Aβ Formation
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Commentary: Aβ N- Terminal Isoforms: Critical contributors in the course of AD pathophysiology
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Background
Chromosome 13 dementia syndromes as models of neurodegeneration
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Background
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Copper selectively triggers β-sheet assembly of an N-terminally truncated amyloid β-peptide beginning with Glu3
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Background
Molecular Biology of Alzheimer’s Dementia and Its Clinical Relevance to Early Diagnosis and New Therapeutic Strategies
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“Simultaneous measurement of beta-amyloid(1-42), total tau, and phosphorylated”
Background
Amyloidogenesis in familial British dementia is associated with a genetic defect on chromosome 13
GHISO, J., VIDAL, R., ROSTAGNO, A., MIRAVALLE, L., HOLTON, J. L., MEAD, S., RÉVÉSZ, T., PLANT, G., & FRANGIONE, B. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06908.x · Cited by 12
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“Deletion of residues one and two and modification of Ab E3 into pyroE3, as found in several truncated and more aggregation prone Ab species in the diseased brain [53,54], showed a decrease in affinity and no”
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Amyloid beta peptide-degrading microbial enzymes and its implication in drug design
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Self-citation
Novel Phosphorylation-State Specific Antibodies Reveal Differential Deposition of Ser26 Phosphorylated Aβ Species in a Mouse Model of Alzheimer’s Disease
Kumar, S., Kapadia, A., Theil, S., Joshi, P., Riffel, F., Heneka, M. T., & Walter, J. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.619639 · Cited by 16
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“In the case of ABri, our results demonstrate that the presence of pE exacerbates the pro-amyloidogenic properties conferred by the FBD mutation, further enhancing the βsheet content, aggregability, and hydrophobicity of the molecule, consistent with the effect of the posttranslational modification in truncated Aβ spec…”
Background
Amniotic tissue in complete hydatidiform moles can be androgenetic
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Inhibition of Glutaminyl Cyclase Ameliorates Amyloid Pathology in an Animal Model of Alzheimer's Disease via the Modulation of γ-Secretase Activity
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Self-citation
Plasma pyroglutamate‐modified amyloid beta differentiates amyloid pathology
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Computational Studies on the Mechanisms of Nonenzymatic Intramolecular Cyclization of the Glutamine Residues Located at N-Termini Catalyzed by Inorganic Phosphate Species
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Ion channel formation by N-terminally truncated Aβ (4–42): relevance for the pathogenesis of Alzheimer's disease
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“The post translationally modified peptides also include different N- and C-terminally truncated Aβ species that have been identified in animal models and AD patients [5,6] and are likely generated by a number of Aβ-degrading enzymes among them neprilysin, insulin degrading- and endothelin converting-enzymes, plasmin a…”
Background

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.
ORCID: Saido, Takaomi C.
Iwatsubo, Takeshi
Venue: Neuroscience Letters
Publisher: Elsevier BV
Published: 1996-09
Volume: 215
Issue: 3
Pages: 173-176
ISSN: 0304-3940 (ISSN-L)
DOI: 10.1016/0304-3940(96)12970-0
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Neuroscience Letters (publishedVersion)
PubMed (publishedVersion)
Funders: Uehara Memorial Foundation
Ministry of Education, Culture, Sports, Science and Technology
Naito Foundation
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
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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Amino- and carboxyl-terminal heterogeneity of β-amyloid peptides deposited in human brain

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