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Mass spectrometric characterization of brain amyloid beta isoform signatures in familial and sporadic Alzheimer’s disease
Open accessAbstract
A proposed key event in the pathogenesis of Alzheimer's disease (AD) is the formation of neurotoxic amyloid beta (Abeta) oligomers and amyloid plaques in specific brain regions that are affected by the disease. The main plaque component is the 42 amino acid isoform of Alphabeta (Abeta1-42), which is thought to initiate plaque formation and AD pathogenesis. Numerous isoforms of Abeta, e.g., Abeta1-42, Abeta1-40 and the 3-pyroglutamate derivate of Abeta3-42 (pGluAbeta3-42), have been detected in the brains of sporadic AD (SAD) and familial AD (FAD) subjects. However, the relative importance of these isoforms in the pathogenesis of AD is not fully understood. Here, we report a detailed study using immunoprecipitation in combination with mass spectrometric analysis to determine the Abeta isoform pattern in the cerebellum, cortex and hippocampus in AD, including subjects with a mutation in the presenilin (M146V) or amyloid precursor protein (KM670/671NL) genes, SAD subjects and non-demented controls. We show that the dominating Abeta isoforms in the three different brain regions analyzed from control, SAD, and FAD are Abeta1-42, pGluAbeta3-42, Abeta4-42 and Abeta1-40 of which Abeta1-42 and Abeta4-42 are the dominant isoforms in the hippocampus and the cortex in all groups analyzed, controls included. No prominent differences in Abeta isoform patterns between FAD and SAD patients were seen, underscoring the similarity in the amyloid pathology of these two disease entities.
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“Among the different Aβ variants, the N-terminally truncated peptide Aβ4–42 is among the most abundant.”
From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [22]
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Metadata
- Authors
- Portelius, E., Bogdanovic, N., Gustavsson, M. K., Volkmann, I., Brinkmalm, G., Zetterberg, H., Winblad, B., & Blennow, K.
- Affiliations
- University of Gothenburg (SE)
- Karolinska Institutet (SE)
- Corresponding author
- Portelius, Erik
- Venue
- Acta Neuropathologica
- Published
- 2010-04-24
- Volume
- 120
- Issue
- 2
- Pages
- 185-193
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC3568930
- OpenAlex
- W2045197448
- Cited by
- 348
- References
- 41
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 27 · 2023: 22 · 2022: 21 · 2021: 25 · 2020: 26 · 2019: 28 · 2018: 26 · 2017: 20 · 2016: 22 · 2015: 31 · 2014: 23 · 2013: 10 · 2012: 16
- FWCI
- 9.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institute on Aging (K08 AG-22228, AG023185, K08AG022228, U01AG016976, P50AG005131, AG-O5131, R01AG023185)
- 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
- Alzheimer's disease, amyloid-beta isoforms, amyloid-beta 42, Aβ40, amyloid-beta oligomers, amyloid plaques, familial Alzheimer's disease, sporadic Alzheimer's disease, amyloid precursor protein mutations, hippocampus, cerebral cortex, cerebellum
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Male, Middle Aged, Peptide Fragments, Mass Spectrometry, Statistics as Topic, Amyloid beta-Peptides, Protein Isoforms, Immunoprecipitation
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