Dominant and differential deposition of distinct β-amyloid peptide species, AβN3(pE), in senile plaques

Saido, Takaomi C; Iwatsubo, Takeshi; Mann, David M.A; Shimada, Hiroyuki; Ihara, Yasuo; Kawashima, Seiichi

doi:10.1016/0896-6273(95)90301-1

Cited by 587Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Dominant and differential deposition of distinct β-amyloid peptide species, AβN3(pE), in senile plaques

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Saido, Takaomi C, Iwatsubo, Takeshi, Mann, David M.A, Shimada, Hiroyuki, Ihara, Yasuo, Kawashima, Seiichi·1995·Neuron

DOI 10.1016/0896-6273(95)90301-1

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Abstract

We analyzed an amino-terminal modification of beta-amyloid (A beta) peptide in brain, using anti-A beta antibodies that distinguish distinct molecular species. Examination of cortical sections from 28 aged individuals with a wide range in senile plaque density revealed that a molecular species distinct from the standard A beta is deposited in the brain in a dominant and differential manner. This modified A beta peptide (A beta N3(pE)) starts at the 3rd aminoterminal residue of the standard A beta, glutamate, converted to pyroglutamate through intramolecular dehydration. Because plaques composed of A beta N3(pE) are present in equivalent or greater densities than those composed of standard A beta bearing the first amino-terminal residue (A beta N1) and because deposition of the former species appears to precede deposition of the latter, as confirmed with specimens from Down's syndrome patients, the processes involved in A beta N3(pE) production and retention may play an early and critical role in senile plaque formation.

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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., 1995
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., 1995
In Emerge, 64 centiloids of amyloid were removed, bringing levels to 21 centiloids by 78 weeks; in Engage, 54 centiloids were removed, bringing levels to 37 centiloids.
“In Emerge, 64 CL of amyloid were removed at the 10mg/kg QW4 dose, bringing levels down to 21 CL by the end of the 78-week study 77 .In Engage, rather less amyloid was removed, 54 CL, bringing amyloid levels to 37 CL at 78 weeks.”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [77]
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 [158]

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Authors: Saido, T. C., Iwatsubo, T., Mann, D. M. A., Shimada, H., Ihara, Y., & Kawashima, S.
Affiliations: Tokyo Metropolitan Institute of Medical Science (JP)
The University of Tokyo (JP)
University of Manchester (GB)
Tokyo Medical University (JP)
ORCID: Saido, Takaomi C
Iwatsubo, Takeshi
Mann, David M.A
Ihara, Yasuo
Venue: Neuron
Publisher: Elsevier BV
Published: 1995-02
Volume: 14
Issue: 2
Pages: 457-466
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/0896-6273(95)90301-1
OpenAlex: W2071310220
Cited by: 587
References: 31
Citations by year: 2026: 10 · 2025: 10 · 2024: 35 · 2023: 12 · 2022: 18 · 2021: 34 · 2020: 19 · 2019: 20 · 2018: 19 · 2017: 22 · 2016: 18 · 2015: 20 · 2014: 30 · 2013: 29 · 2012: 28
FWCI: 11.04
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 6741 d)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
Funders: Naito Foundation
Ministry of Education, Culture, Sports, Science and Technology
Ono Medical Research 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, pyroglutamic acid, amyloid plaques, amyloid deposition, Alzheimer's disease, Down syndrome, intramolecular dehydration, anti-amyloid antibodies
MeSH terms: Adult, Aged, Aged, 80 and over, Alzheimer Disease, Amino Acid Sequence, Antibodies, Antibody Specificity, Brain, Down Syndrome, Female, Humans, Immune Sera, Male, Middle Aged, Molecular Sequence Data, Oligopeptides, Organ Specificity, Amyloid beta-Peptides

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Dominant and differential deposition of distinct β-amyloid peptide species, AβN3(pE), in senile plaques

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