Journal
NEUROBIOLOGY OF AGING
Volume 32, Issue 11, Pages 1990-1993Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2009.11.019
Keywords
LRRK2; Variants; Alzheimer's disease
Categories
Funding
- National Medical Research Council
- National Neuroscience Institute
- Singapore General Hospital
- Singapore Millennium Foundation
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Overlapping neurodegenerative pathologies (including Alzheimer's disease, AD) have been described in Parkinson's disease (PD) patients with leucine-rich repeat kinase-2 (LRRK2) mutations. We analyzed a LRRK2 PD (R1628P) risk variant in a group of 885 subjects comprising of AD and controls. The frequency of the R1628P allele was higher in AD compared to controls (3.5% vs. 1.6%, OR 2.3, 95 CI 1.2-4.4, p = 0.018). In vitro, the mean percentage of apoptosis and cell death observed for the R1628P transfected human cell lines was higher compared to wild type 21.8 +/- 1.9, vs. 17.1 +/- 1.3, p < 0.05, 30.2 +/- 2.2 vs. 25.7 +/- 1.3, p < 0.05). The LRRK2 R1628P variant increases the risk of AD in our population and our in vitro findings suggest that it is a functional variant and predisposes to apoptosis. (C) 2009 Elsevier Inc. All rights reserved.
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