Selected LDLR and APOE Polymorphisms Affect Cognitive and Functional Response to Lipophilic Statins in Alzheimer ’s Disease

AbstractEffects of statins over clinical changes in Alzheimer ’s disease (AD) are usually non-significant, but epistatic interactions between genetic variants involved in cholesterol metabolism could be important for such effects. We aimed to investigate whetherLDLR single-nucleotide polymorphisms rs11669576 (LDLR8), rs5930 (LDLR10), and rs5925 (LDLR13) are associated with cognitive and functional changes in AD, while also consideringAPOE haplotypes and lipid-lowering treatment with lipophilic statins for stratification. Consecutive outpatients with late-onset AD were screened with cognitive tests, while caregivers scored functionality and caregiver burden, with prospective neurotranslational correlations documented for 1  year. For 179 patients, minor allele frequencies were 0.078 for rs11669576–A (14.5% heterozygotes), 0.346 for rs5930–A (42.5% heterozygotes), and 0.444 for rs5925–C (56.4% heterozygotes), all in Hardy-Weinberg equilibrium; 134 patients had hypercholesterolemia, and 133 used lipophilic statin s. Carriers of rs11669576–G had faster cognitive decline, while functional decline was slower for carriers of rs11669576–A who used lipophilic statins.APOE- ε4 carriers who also carried rs5930–AA had improved caregiver burden, while carriers of haplotypes that included rs5930–AG had worse cognitive and functional outcomes, though carriers of the A allele of rs5930 had better cognitive and functional response to lipophilic statins.APOE- ε4 non-carriers...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research