Targeting small Aβ oligomers: the solution to an Alzheimer's disease conundrum?
Abstract
Amyloid beta (Abeta) is a small self-aggregating peptide produced at low levels by normal brain metabolism. In Alzheimer's disease (AD), self-aggregation of Abeta becomes rampant, manifested most strikingly as the amyloid fibrils of senile plaques. Because fibrils can kill neurons in culture, it has been argued that fibrils initiate the neurodegenerative cascades of AD. An emerging and different view, however, is that fibrils are not the only toxic form of Abeta, and perhaps not the neurotoxin that is most relevant to AD: small oligomers and protofibrils also have potent neurological activity. Immuno-neutralization of soluble Abeta-derived toxins might be the key to optimizing AD vaccines that are now on the horizon.
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The particular toxic substance(s) within NPs still have not been completely characterized.
“The particular toxic substance(s) within NPs still have not been completely characterized (90, 103, 278), but NPs represent a nidus in which extracellular plaque substance(s) seem to induce intracellular degenerative changes with tau pathology (18, 50, 279-281).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [278]
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Temporal memory deficits in Alzheimer’s mouse models: Rescue by genetic deletion of BACE1
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Amyloid β-Protein Dimers Rapidly Form Stable Synaptotoxic Protofibrils
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Synaptic Changes in Alzheimer's Disease
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“Human A is neurotoxic when added to cultures of neural cells or tissue sections (Pike et al., 1993; Yankner, 1996; Klein et al., 2001), injected into the brain (Geula et al., 1998), or produced in neurons of transgenic mice (Games et al., 1995; Masliah et al., 1996, 2001; Nalbantoglu et al., 1997;…”
BackgroundInfluentialβ-Amyloid Immunotherapy Prevents Synaptic Degeneration in a Mouse Model of Alzheimer's Disease
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Alzheimer’s disease, cerebrovascular disease, and the β-amyloid cascade
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Insulin Receptor Dysfunction Impairs Cellular Clearance of Neurotoxic Oligomeric Aβ
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Self-citationWhy is the amyloid beta peptide of Alzheimer’s disease neurotoxic?
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ATP-binding cassette transporter A7 (ABCA7) loss of function alters Alzheimer amyloid processing
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- Authors
- Klein, W.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Klein, W
- ORCID
- Klein, W
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2001-04-01
- Volume
- 24
- Issue
- 4
- Pages
- 219-224
- ISSN
- 0166-2236 (ISSN-L)
- OpenAlex
- W1972567838
- Cited by
- 989
- References
- 47
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 26 · 2023: 19 · 2022: 16 · 2021: 19 · 2020: 29 · 2019: 21 · 2018: 29 · 2017: 36 · 2016: 38 · 2015: 39 · 2014: 40 · 2013: 39 · 2012: 71
- FWCI
- 31.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1p01ag015501-01)
- National Institute on Aging (AG-13499, AG-15501, R01AG013499)
- 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, protofibrils, amyloid fibrils, neurotoxicity, amyloid plaques, neurodegeneration, immunization, Alzheimer's disease vaccine, peptide self-aggregation
- MeSH terms
- Alzheimer Disease, Animals, Antibodies, Hippocampus, Mice, Transgenic, Peptide Fragments, Vaccines, Signal Transduction, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Synaptophysin, Long-Term Potentiation, Mice, Plaque, Amyloid
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