Aβ oligomers inhibit synapse remodelling necessary for memory consolidation
Open accessAbstract
Extensive research has implicated the amyloid-β protein (Aβ) in the aetiology of Alzheimer's disease (AD). This protein has been shown to produce memory deficits when injected into rodent brain and in mouse models of AD Aβ production is associated with impaired learning and/or recall. Here we examined the effects of cell-derived SDS-stable 7PA2-derived soluble Aβ oligomers on consolidation of avoidance learning. At 0, 3, 6, 9 or 12h after training, animals received an intracerebroventricular injection of Aβ-containing or control media and recall was tested at 24 and 48 h. Immediately after 48 h recall animals were transcardially perfused and the brain removed for sectioning and EM analysis. Rats receiving injections of Aβ at 6 or 9h post-training showed a significant impairment in memory consolidation at 48 h. Importantly, impaired animals injected at 9h had significantly fewer synapses in the dentate gyrus. These data suggest that Aβ low-n oligomers target specific temporal facets of consolidation-associated synaptic remodelling whereby loss of functional synapses results in impaired consolidation.
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Soluble oAβ induced a significant loss of colocalized synapsin- and PSD95-immunoreactive puncta in wild-type mice within 72 h.
“Soluble oAβ induced a significant loss of colocalized synapsin- and PSD95-immunoreactive puncta in WT mice within 72 h (Fig. 3A, left panel) (17).”
From Complement and microglia mediate early synapse loss in Alzheimer mouse models (2016) · cites this paper as [17]
The Results (page unavailable) report significantly reduced dentate-gyrus synapse density after soluble Aβ-containing medium was infused into rats 9 hours after training, with assessment at 48 hours. This supports an Aβ-associated synapse reduction within 72 hours, but the paper studied rats, not wild-type mice, and counted synapses by electron microscopy rather than colocalized synapsin- and PSD95-immunoreactive puncta. (LLM, conf=0.88)
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- Authors
- Freir, D. B., Fedriani, R., Scully, D., Smith, I. M., Selkoe, D. J., Walsh, D. M., & Regan, C. M.
- Affiliations
- University College Dublin (IE)
- Brigham and Women's Hospital (US)
- Corresponding author
- Walsh, Dominic M.
- Regan, Ciaran M.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 32
- Issue
- 12
- Pages
- 2211-2218
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC2891223
- OpenAlex
- W2066418720
- Cited by
- 85
- References
- 59
- Citations by year
- 2026: 1 · 2025: 3 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 6 · 2017: 8 · 2016: 11 · 2015: 5 · 2014: 8 · 2013: 9 · 2012: 9
- FWCI
- 7.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- European Community 7th Framework Programme (200611)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- amyloid-beta oligomers, memory consolidation, avoidance learning, Alzheimer's disease, dentate gyrus, synaptic loss, intracerebroventricular administration
- MeSH terms
- Animals, Avoidance Learning, Cricetulus, Cricetinae, Humans, Male, Memory, Memory Disorders, Neural Inhibition, Neuronal Plasticity, Synapses, Amyloid beta-Peptides, CHO Cells, Rats, Wistar, Rats
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