Cited by 94Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Age-related accumulation of Reelin in amyloid-like deposits

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Knuesel, Irene, Nyffeler, Myriel, Mormède, Cecile, Muhia, Mary, Meyer, Urs, Pietropaolo, Susanna, Yee, Benjamin K., Pryce, Christopher R. +3 more·2009·Neurobiology of Aging

Abstract

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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Crossref · 10.1016/j.neurobiolaging.2007.08.011

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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)
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
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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