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Aβ40 Oligomers Identified as a Potential Biomarker for the Diagnosis of Alzheimer's Disease
Open accessAbstract
Alzheimer's Disease (AD) is the most prevalent form of dementia worldwide, yet the development of therapeutics has been hampered by the absence of suitable biomarkers to diagnose the disease in its early stages prior to the formation of amyloid plaques and the occurrence of irreversible neuronal damage. Since oligomeric Aβ species have been implicated in the pathophysiology of AD, we reasoned that they may correlate with the onset of disease. As such, we have developed a novel misfolded protein assay for the detection of soluble oligomers composed of Aβ x-40 and x-42 peptide (hereafter Aβ40 and Aβ42) from cerebrospinal fluid (CSF). Preliminary validation of this assay with 36 clinical samples demonstrated the presence of aggregated Aβ40 in the CSF of AD patients. Together with measurements of total Aβ42, diagnostic sensitivity and specificity greater than 95% and 90%, respectively, were achieved. Although larger sample populations will be needed to confirm this diagnostic sensitivity, our studies demonstrate a sensitive method of detecting circulating Aβ40 oligomers from AD CSF and suggest that these oligomers could be a powerful new biomarker for the early detection of AD.
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“These assays, which can be many orders of magnitude more sensitive than ELISAs, have established an AD-dependent accumulation of oligomers in human CSF (Fukumoto et al., 2010; Gao et al., 2010; Georganopoulou et al., 2005; Haes et al., 2005).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Gao et al., 2010
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1 retracted
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Metadata
- Authors
- Gao, C. M., Yam, A. Y., Wang, X., Magdangal, E., Salisbury, C., Peretz, D., Zuckermann, R. N., Connolly, M. D., Hansson, O., Minthon, L., Zetterberg, H., Blennow, K., Fedynyshyn, J. P., & Allauzen, S.
- Affiliations
- Lund University (SE)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Fedynyshyn, Joseph P.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-12-30
- Volume
- 5
- Issue
- 12
- Pages
- e15725
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3012719
- OpenAlex
- W2135057867
- Cited by
- 105
- References
- 39
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 8 · 2018: 4 · 2017: 11 · 2016: 9 · 2015: 10 · 2014: 17 · 2013: 13 · 2012: 12
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- 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, Aβ40, amyloid-beta 42, cerebrospinal fluid biomarkers, early diagnosis, amyloid plaques, sensitivity and specificity
- MeSH terms
- Aged, Alzheimer Disease, Epitopes, Brain, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Humans, Middle Aged, Models, Chemical, Molecular Conformation, Peptide Fragments, Peptides, Protein Conformation, Sensitivity and Specificity, Biomarkers, Amyloid beta-Peptides
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