Beta-amyloid controls altered Reelin expression and processing in Alzheimer's disease
Arancha Botella-López1, Inmaculada Cuchillo-Ibáñez, Tiziana Cotrufo
1Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, E-03550, Spain.
Neurobiology of Disease
|December 23, 2009
Summary
Reelin protein levels and processing are altered in Down syndrome and Alzheimer's disease, linked to beta-amyloid. This suggests Reelin dysfunction contributes to these neurodegenerative conditions.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Reelin is a crucial glycoprotein for synaptic function and memory formation in the adult brain.
- Previous research indicated altered cerebral Reelin expression in Alzheimer's disease (AD).
- Down syndrome (DS) involves an extra chromosome 21, leading to beta-amyloid overexpression.
Purpose of the Study:
- To investigate Reelin expression and processing alterations in Down syndrome (DS) and other amyloid-related conditions.
- To explore the impact of beta-amyloid on Reelin levels and post-translational modifications.
Main Methods:
- Analysis of Reelin protein and mRNA levels in frontal cortex from adult and fetal DS samples.
- Examination of Reelin in Tg2576 transgenic mice overexpressing mutant human amyloid precursor protein.
- In vitro studies involving Abeta42 treatment of SH-SY5Y neuroblastoma cells.
- Assessment of Reelin glycosylation patterns in AD patients and treated cell lines.
Main Results:
- Pronounced changes in Reelin protein and mRNA were observed in the frontal cortex of adult DS.
- Increased levels of full-length Reelin and a 310-kDa fragment were detected in fetal DS cortical extracts.
- Overexpression of mutant amyloid precursor protein and in vitro Abeta42 treatment elevated Reelin fragment levels.
- Altered Reelin glycosylation patterns were found in AD patients and Abeta42-treated cells, indicating beta-amyloid-induced processing changes.
Conclusions:
- Reelin expression and processing are significantly altered in Down syndrome, a condition associated with beta-amyloid overexpression.
- Beta-amyloid appears to trigger changes in Reelin processing and glycosylation, as observed in AD and DS.
- These findings suggest a role for Reelin dysfunction in the pathogenesis of amyloid-related conditions like AD and DS.
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