RESUMO
Cathepsin D (CTSD) is a gene involved in amyloid precursor protein processing and is considered a candidate for Alzheimer's disease (AD). The aim of the current study was to examine if variation in CTSD increases the risk of AD. We performed a candidate-gene analysis in a population-based cohort study (N=7983), and estimated the effect of CTSD on the risk of AD. Additionally, a large meta-analysis was performed incorporating our data and previously published data. The T-allele of CTSD rs17571 was associated with an increased risk of AD (p-value 0.007) in the Rotterdam Study. This association was predominantly found in APOE ε4 noncarriers. A meta-analysis of previously published data showed a significantly increased risk of AD in carriers of the T-allele of rs17571 (OR 1.22, 95% CI 1.03-1.44), irrespective of APOE ε4 carrier status. This study adds to the evidence that CTSD increases the risk of AD, although the effect size is moderate.
Assuntos
Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Catepsina D/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Medicina Baseada em Evidências/tendências , Feminino , Humanos , Estudos Longitudinais , Masculino , Polimorfismo de Nucleotídeo Único/genética , Fatores de RiscoRESUMO
Apolipoprotein E (APOE) is consistently associated with dementia in the general population. Findings on the role of this gene in persons with Down's syndrome (DS) are inconclusive. We studied the effects of APOE on mortality and dementia in a longitudinal prospective study of a large population-based sample of persons with DS (n=425), demented and non-demented. There was evidence that APOE epsilon4 is correlated with the rate of decline in the social competence rating scale (SRZ) (p=0.04). In our population, we found overall a modest but not statistical significant effect on the prevalence of dementia (OR=1.57, 95%CI: 0.87-2.82). We did observed a significant long-term effect on the incidence of dementia (HR=4.66, 95%CI: 1.35-16.14), but for those with a follow-up less than 3 years the risk was not significantly increased: HR=0.83 (95%CI 0.35-1.94). When pooling our data in a meta-analysis, the APOE epsilon4 allele shows a 1.59-fold (95%CI: 1.19-2.12) increase in risk of dementia in persons with DS. We conclude that APOE is influencing the risk of dementia in persons with DS.