Neurobiology of aging, 2009-05, Vol.30 (5), p.697-716
2009
Details
- Autor(en) / Beteiligte
- Titel
- Age-related accumulation of Reelin in amyloid-like deposits
- Ist Teil von
- Neurobiology of aging, 2009-05, Vol.30 (5), p.697-716
- Ort / Verlag
- London: Elsevier Inc
- Erscheinungsjahr
- 2009
- Link zum Volltext
- Quelle
- Elsevier ScienceDirect Journals
- Beschreibungen/Notizen
- 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 Aβ 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0197-4580eISSN: 1558-1497DOI: 10.1016/j.neurobiolaging.2007.08.011Titel-ID: cdi_proquest_miscellaneous_67053110
- Format
- –
- Schlagworte
- 3xTg-AD mice, Aging - metabolism, Aging - pathology, Alzheimer Disease - metabolism, Alzheimer Disease - pathology, Alzheimer Disease - physiopathology, Alzheimer's disease, Amyloid beta-Peptides - metabolism, Amyloid beta-Protein Precursor - genetics, Animals, Biological and medical sciences, Callithrix, Callithrix jacchus, Cell Adhesion Molecules, Neuronal - analysis, Cell Adhesion Molecules, Neuronal - metabolism, Dab1, Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases, Development. Senescence. Regeneration. Transplantation, Entorhinal cortex, Episodic-like memory, Extracellular Matrix Proteins - analysis, Extracellular Matrix Proteins - metabolism, F4/80, Female, Fundamental and applied biological sciences. Psychology, GABAergic interneurons, Gene Knock-In Techniques, GFAP, Hippocampus, Hippocampus - metabolism, Hippocampus - pathology, Immunohistochemistry, Internal Medicine, Male, Medical sciences, Memory Disorders - metabolism, Memory Disorders - pathology, Memory Disorders - physiopathology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mus musculus, Nerve Degeneration - metabolism, Nerve Degeneration - pathology, Nerve Degeneration - physiopathology, Nerve Tissue Proteins - analysis, Nerve Tissue Proteins - metabolism, Neuroinflammation, Neurology, Neurons - metabolism, Neurons - pathology, Piriform cortex, Plaque, Amyloid - metabolism, Plaque, Amyloid - pathology, PolyIC, Radial arm maze, ras Proteins - genetics, Rats, Rats, Wistar, Rattus norvegicus, Risk Factors, Serine Endopeptidases - analysis, Serine Endopeptidases - metabolism, Stratum lacunosum-moleculare, SynGAP, tau Proteins - genetics, Vertebrates: nervous system and sense organs