Quantification of Modified Amyloid β Peptides in Alzheimer Disease and Down Syndrome Brains

Hosoda, Ritsuko; Saido, Takaomi C.; Otvos, Laszlo; Arai, Takao; Mann, David M.A.; Lee, Virginia M.-Y.; Trojanowski, John Q.; Iwatsubo, Takeshi

doi:10.1097/00005072-199811000-00012

Cited by 80Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Quantification of Modified Amyloid β Peptides in Alzheimer Disease and Down Syndrome Brains

Hosoda, Ritsuko, Saido, Takaomi C., Otvos, Laszlo, Arai, Takao, Mann, David M.A., Lee, Virginia M.-Y., Trojanowski, John Q., Iwatsubo, Takeshi·1998·Journal of Neuropathology and Experimental Neurology

DOI 10.1097/00005072-199811000-00012

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Abstract

To gain insights into the different forms of modified amyloid beta peptides (A beta) in the Alzheimer disease (AD) and Down syndrome (DS) brain, we used two-site ELISAs with antibodies specific for isomerized (i.e. A beta with L-isoaspartate at positions 1 and 7) and pyroglutamate-modified (i.e. A beta beginning with pyroglutamate at position 3) forms of A beta to quantitate the levels of these different A beta peptides in formic acid extracts of AD and DS frontal cortex. Despite variations in the proportions of distinct forms of A beta in AD and DS frontal cortex, the major species of A beta in these samples were A betaN3(pyroGlu)-42 as well as A beta x-42 (where x is a residue at position 2 or less in A beta), whereas isomerized A beta was a minor species. Further, the levels of isomerized and pyroglutamate-modified forms of A beta terminating at amino acid 42 were higher than those ending at amino acid 40. The abundance of the distinct forms of A beta reported here in formic acid extracts of AD and DS frontal cortex suggests that these A beta species could play important roles in the deposition of A beta in AD and DS brains.

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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 Hosoda et al., 1998
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 Hosoda et al., 1998

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Authors: Hosoda, R., Saido, T. C., Otvos, L., Arai, T., Mann, D. M. A., Lee, V. M.-Y., Trojanowski, J. Q., & Iwatsubo, T.
Affiliations: Tokyo University of Science (JP)
RIKEN Center for Brain Science (JP)
University of Manchester (GB)
University of Pennsylvania (US)
Japan Science and Technology Agency (JP)
Corresponding author: Iwatsubo, Takeshi
ORCID: Saido, Takaomi C.
Mann, David M.A.
Lee, Virginia M.-Y.
Trojanowski, John Q.
Iwatsubo, Takeshi
Venue: Journal of Neuropathology and Experimental Neurology
Publisher: Oxford University Press (OUP)
Published: 1998-11
Volume: 57
Issue: 11
Pages: 1089-1095
ISSN: 0022-3069 (ISSN-L)
DOI: 10.1097/00005072-199811000-00012
OpenAlex: W2017898906
Cited by: 79
References: 0
Citations by year: 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 7 · 2018: 8 · 2017: 5 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 4 · 2012: 3
FWCI: 1.84
Type: journal article
Language: en
Open access: closed
Locations: Journal of Neuropathology & Experimental Neurology (publishedVersion)
PubMed (publishedVersion)
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, Alzheimer's disease, Down syndrome, frontal cortex, amyloid deposition, peptide quantification
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Down Syndrome, Enzyme-Linked Immunosorbent Assay, Female, Frontal Lobe, Humans, Immunohistochemistry, Male, Middle Aged, Peptide Fragments, Immunoblotting, Amyloid beta-Peptides

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Quantification of Modified Amyloid β Peptides in Alzheimer Disease and Down Syndrome Brains

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