Age-related accumulation of Reelin in amyloid-like deposits

Irene Knuesel, Myriel Nyffeler, Cecile Mormède, Mary Muhia, Urs Meyer, Susanna Pietropaolo, Benjamin K. Yee, Christopher R. Pryce, Frank M. LaFerla, Aline Marighetto, Joram Feldon
Neurobiology of Aging. 2009-05-01; 30(5): 697-716
DOI: 10.1016/j.neurobiolaging.2007.08.011

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1. Neurobiol Aging. 2009 May;30(5):697-716. Epub 2007 Sep 27.

Age-related accumulation of Reelin in amyloid-like deposits.

Knuesel I(1), Nyffeler M, Mormède C, Muhia M, Meyer U, Pietropaolo S, Yee BK,
Pryce CR, LaFerla FM, Marighetto A, Feldon J.

Author information:
(1)Institute of Pharmacology and Toxicology, University of Zurich,
Winterthurerstrasse 190, 8057 Zurich, Switzerland.

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.

DOI: 10.1016/j.neurobiolaging.2007.08.011
PMID: 17904250 [Indexed for MEDLINE]


Auteurs Bordeaux Neurocampus