CLU rs11136000 promotes early cognitive decline in Parkinson's disease

Background The C allele of the rs11136000 genetic variant of the clusterin gene has been associated with increased risk of Alzheimer's disease. However, a comprehensive characterization of the role of this genetic variant in early cognitive deterioration in PD is lacking. Methods Using the Parkinson's Progression Markers Initiative database, we compared baseline and 5-year cognitive performance between high-risk and low-risk clusterin genotypes. Results At baseline, recently diagnosed and drug-naive de novo PD patients with the high-risk clusterin genotype showed lower cognitive scores in memory and executive function tests. These differences were even higher at the 5-year follow-up, when they showed a higher prevalence of clinically diagnosed mild cognitive impairment or dementia. They also showed cortical thinning at baseline and increased annual thinning in frontal and posterior cortical regions. Discussion Our results provide evidence of this clusterin genotype promoting early cognitive deterioration in PD, but further research is needed to delineate the specific neurodegenerative pathways underlying this clinical association. (c) 2020 International Parkinson and Movement Disorder Society