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

Autor(es)

de Oliveira, Fabricio Ferreira ^[1] ; Chen, Elizabeth Suchi ^[2] ; Smith, Marilia Cardoso ^[2] ; Ferreira Bertolucci, Paulo Henrique ^[1]

Afiliação do(s) autor(es)

^[1] Fed Univ Sao Paulo UNIFESP, Escola Paulista Med, Dept Neurol & Neurosurg, Sao Paulo, SP - Brazil

^[2] Fed Univ Sao Paulo UNIFESP, Escola Paulista Med, Dept Morphol & Genet, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF MOLECULAR NEUROSCIENCE; v. 70, n. 10 MAY 2020.
• Citações Web of Science: 1

Resumo

Effects 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 whether LDLR single-nucleotide polymorphisms rs11669576 (LDLR8), rs5930 (LDLR10), and rs5925 (LDLR13) are associated with cognitive and functional changes in AD, while also considering APOE 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 statins. Carriers of rs11669576-G had faster cognitive decline, while functional decline was slower for carriers of rs11669576-A who used lipophilic statins. APOE-epsilon 4 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-epsilon 4 non-carriers who carried rs5925-TT had slower cognitive decline, while lipophilic statins protected carriers of the other genotypes. We preliminarily conclude that reportedly protective variants of LDLR and APOE against risk of AD also slowed cognitive decline, regardless of cholesterol variations, while therapy with lipophilic statins might benefit carriers of specific genetic variants. (AU)

• Processo FAPESP: 15/18125-0 - Análise comparativa de marcadores liquóricos e séricos na demência com corpúsculos de Lewy e na demência da Doença de Alzheimer
• Beneficiário: Paulo Henrique Ferreira Bertolucci
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/10109-5 - Análise comparativa de marcadores liquóricos e séricos na demência com corpúsculos de Lewy e na demência da Doença de Alzheimer
• Beneficiário: Fabricio Ferreira de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado