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Soluble fibrillar oligomer levels are elevated in Alzheimer's disease brain and correlate with cognitive dysfunction
Open accessAbstract
Recent evidence has suggested a role for soluble oligomeric Abeta species in the pathology of Alzheimer's disease (AD). Fibrillar plaque deposits are present in non-demented individuals and levels of soluble Abeta correlate better with cognitive dysfunction in AD and transgenic mouse models. We have previously reported that there are at least two conformationally distinct types of Abeta oligomers: prefibrillar oligomers that are kinetic intermediates in fibril assembly reactions and are specifically recognized by A11 antibody and fibrillar oligomers that may represent fibril seeds or small pieces of fibrils and are recognized by a fibril specific antibody, OC. We have examined the levels of these two types of oligomers in the PBS soluble fraction of brain tissue from control cases, cases with senile degenerative changes (SDC) and AD patients. We found that the levels of soluble fibrillar oligomers detected by OC antibody are significantly elevated in multiple brain regions of AD patients. The elevated fibrillar oligomer levels were found not to be an artifact of tissue homogenization, nor a result of increased Abeta or APP levels. The concentration of fibrillar oligomers in adjacent brain regions of the same patient can vary widely and were not detected in post-mortem cerebrospinal fluid. In contrast, the level of prefibrillar oligomers are variable in both AD and age matched controls, indicating that they are not correlated with cognitive dysfunction and suggesting that they precede dementia in AD. Significant correlations were found between the levels of fibrillar oligomers and cognitive decline (MMSE scores) as well as the neuropathological hallmarks of AD. These results indicate that fibrillar oligomers may play a key role in the pathology of AD and may be a new target for diagnostic and therapeutic development.
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“soluble oligomers correlate with cognitive decline (Mini Mental State Examination (MMSE) scores) and tangle stage (20).”
From APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease (2012) · cites this paper as [20]
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Metadata
- Authors
- Tomic, J. L., Pensalfini, A., Head, E., & Glabe, C. G.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Glabe, Charles G.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 35
- Issue
- 3
- Pages
- 352-358
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC2725199
- OpenAlex
- W1970016175
- Cited by
- 336
- References
- 39
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 9 · 2023: 12 · 2022: 16 · 2021: 16 · 2020: 13 · 2019: 13 · 2018: 27 · 2017: 18 · 2016: 20 · 2015: 27 · 2014: 29 · 2013: 35 · 2012: 35
- FWCI
- 19.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Aging (P01AG000538, AG 00538)
- 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 oligomers, prefibrillar oligomers, soluble oligomers, cognitive impairment, brain tissue, neuropathology, diagnostic biomarkers
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cognition Disorders, Female, Humans, Male, Psychiatric Status Rating Scales, Receptors, Cell Surface, Immunoblotting, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Fibrillar Collagens, Protease Nexins
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