Age-related accumulation of Reelin in amyloid-like deposits

Irene Knuesel, Myriel Nyffeler, Cecile Mormède, Mary Muhia, Urs Meyer, Susanna Pietropaolo, Kay Yan Benjamin Yee, Christopher R. Pryce, Frank M. LaFerla, Aline Marighetto, Joram Feldon

Research output: Journal article publicationJournal articleAcademic researchpeer-review

67 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)697-716
Number of pages20
JournalNeurobiology of Aging
Volume30
Issue number5
DOIs
Publication statusPublished - 1 May 2009
Externally publishedYes

Keywords

  • 3xTg-AD mice
  • Alzheimer's disease
  • Callithrix jacchus
  • Dab1
  • Entorhinal cortex
  • Episodic-like memory
  • F4/80
  • GABAergic interneurons
  • GFAP
  • Hippocampus
  • Immunohistochemistry
  • Mus musculus
  • Neuroinflammation
  • Piriform cortex
  • PolyIC
  • Radial arm maze
  • Rattus norvegicus
  • Stratum lacunosum-moleculare
  • SynGAP

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology
  • Clinical Neurology

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