Age-related accumulation of Reelin in amyloid-like deposits
Open accessAbstract
Accumulating evidence suggest that alterations in Reelin-mediated signaling may contribute to neuronal dysfunction associated with Alzheimer's disease (AD), the most common form of senile dementia. However, limited information is available on the effect of age, the major risk factor of AD, on Reelin expression. Here, we report that normal aging in rodents and primates is accompanied by accumulation of Reelin-enriched proteinous aggregates in the hippocampal formation that are related to the loss of Reelin-expressing neurons. Both phenomena are associated with age-related memory impairments in wild-type mice. We provide evidence that normal aging involves loss of Reelin neurons, reduced production and elimination of the extracellular deposits, whereas a prenatal immune challenge or the expression of AD-causing gene products, result in earlier, higher, and more persistent levels of Reelin-positive deposits. These aggregates co-localize with non-fibrillary amyloid-plaques, potentially representing oligomeric Abeta species. Our findings suggest that elevated Reelin plaque load creates a precursor condition for senile plaque deposition and may represent a critical risk factor for sporadic AD.
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Altered cleavage may enhance the adsorption of Reelin into Aβ plaques, which would further exacerbate the deficit in Reelin signaling.
“This altered cleavage may enhance the adsorption of Reelin into A plaques (90), which would further exacerbate the deficit in Reelin signaling.”
From Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses (2017) · cites this paper as [90]
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“This altered cleavage may enhance the adsorption of Reelin into A plaques (90), which would further exacerbate the deficit in Reelin signaling.”
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- Authors
- Knuesel, I., Nyffeler, M., Mormède, C., Muhia, M., Meyer, U., Pietropaolo, S., Yee, B. K., Pryce, C. R., LaFerla, F. M., Marighetto, A., & Feldon, J.
- Affiliations
- ETH Zurich (CH)
- University of California, Irvine (US)
- Université Bordeaux-I (FR)
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 30
- Issue
- 5
- Pages
- 697-716
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2086814010
- Cited by
- 94
- References
- 72
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 12 · 2015: 3 · 2014: 6 · 2013: 9 · 2012: 12
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.zora.uzh.ch
- Licence
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- 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
- reelin, Alzheimer's disease, normal aging, hippocampus, memory impairment, amyloid plaques, amyloid-beta oligomers, prenatal immune challenge, senile dementia
- MeSH terms
- Reelin Protein, Aging, Alzheimer Disease, Animals, Callithrix, Female, Hippocampus, Male, Memory Disorders, Mice, Inbred C57BL, Mice, Transgenic, Nerve Degeneration, Nerve Tissue Proteins, Neurons, Risk Factors, Serine Endopeptidases, Cell Adhesion Molecules, Neuronal, Amyloid beta-Peptides, Extracellular Matrix Proteins, Amyloid beta-Protein Precursor, tau Proteins, Rats, Wistar, ras Proteins, Mice, Rats, Gene Knock-In Techniques, Plaque, Amyloid
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