LRRK2 variant associated with Alzheimer's disease

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.