Reelin delays amyloid-beta fibril formation and rescues cognitive deficits in a model of Alzheimer’s disease
Open accessAbstract
Reelin is an extracellular matrix protein that is crucial for neural development and adult brain plasticity. While the Reelin signalling cascade has been reported to be associated with Alzheimer's disease (AD), the role of Reelin in this pathology is not understood. Here we use an in vitro approach to show that Reelin interacts with amyloid-β (Aβ42) soluble species, delays Aβ42 fibril formation and is recruited into amyloid fibrils. Furthermore, Reelin protects against both the neuronal death and dendritic spine loss induced by Aβ42 oligomers. In mice carrying the APP(Swe/Ind) mutation (J20 mice), Reelin overexpression delays amyloid plaque formation and rescues the recognition memory deficits. Our results indicate that by interacting with Aβ42 soluble species, delaying Aβ plaque formation, protecting against neuronal death and dendritic spine loss and preventing AD cognitive deficits, the Reelin pathway deserves consideration as a therapeutic target for the treatment of AD pathogenesis.
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Enhancing Reelin signaling by either exogenous supplementation of Reelin or reversing the ApoER2 splicing deficit with antisense oligonucleotides can improve the cognitive performance of AD mice.
“Enhancing Reelin signaling by either exogenous supplementation of Reelin (95) or reversing the ApoER2 splicing deficit with antisense oligonucleotides (91) can improve the cognitive performance of AD mice in a murine model of AD.”
From Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses (2017) · cites this paper as [95]
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- Authors
- Pujadas, L., Rossi, D., Andrés, R., Teixeira, C. M., Serra-Vidal, B., Parcerisas, A., Maldonado, R., Giralt, E., Carulla, N., & Soriano, E.
- Affiliations
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Institute for Research in Biomedicine (ES)
- Universitat Pompeu Fabra (ES)
- Corresponding author
- Soriano, Eduardo
- ORCID
- Venue
- Nature Communications
- Published
- 2014-03-06
- Volume
- 5
- Issue
- 1
- Pages
- 3443-3443
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2069124369
- Cited by
- 129
- References
- 47
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 9 · 2022: 9 · 2021: 6 · 2020: 17 · 2019: 12 · 2018: 9 · 2017: 12 · 2016: 23 · 2015: 11 · 2014: 5
- FWCI
- 11.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Ministerio de Ciencia e Innovación
- 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, amyloid-beta, amyloid plaques, dendritic spine loss, neuronal cell death, therapeutic target, extracellular matrix proteins
- MeSH terms
- Reelin Protein, Alzheimer Disease, Amyloid, Animals, Behavior, Animal, Brain, Cells, Cultured, Cognition Disorders, Disease Models, Animal, Humans, Male, Mice, Transgenic, Nerve Tissue Proteins, Peptide Fragments, Protein Binding, Serine Endopeptidases, Blotting, Western, Cell Adhesion Molecules, Neuronal, Amyloid beta-Peptides, Extracellular Matrix Proteins, Amyloid beta-Protein Precursor, Microscopy, Electron, Transmission, Dendritic Spines, Mice, HEK293 Cells, Plaque, Amyloid
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