Late-onset Alzheimer's disease (LOAD) is a multifactorial neurodegenerative disorder that corresponds to most Alzheimer's disease (AD) cases. Inflammation is frequently related to AD, whereas microglial cells are the major phagocytes in the brain and mediate the removal of Aβ peptides. Microglial cell dsyregulation might contribute to the formation of amyloid plaques, a hallmark of AD. Genome-wide association studies have reported genetic loci associated with the inflammatory pathway involved in AD. Among them, rs3865444 CD33, rs3764650 ABCA7, rs6656401 CR1, and rs610932 MS4A6A variants in microglial genes are associated with LOAD. These variants are proposed to participate in the clearance of Aβ peptides. However, their association with LOAD was not validated in all case-control studies. Thus, the present work aimed to assess the involvement of CD33 (rs3865444), ABCA7 (rs3764650), CR1 (rs6656401), and MS4A6A (rs610932) with LOAD in a sample from southeastern Brazil. The genotype frequencies were assessed in 79 AD patients and 145 healthy elders matched for sex and age. We found that rs3865444 CD33 acts as a protective factor against LOAD. These results support a role for the inflammatory pathway in LOAD.

Although several alleles of susceptibility to Alzheimer's disease (AD) have been studied in the last decades, few polymorphisms have been considered as risk factors for the disease. Among them, the APOE-e4 allele appears to be the major genetic risk factor for the onset of the disease. However, it is important to confirm the potential susceptibility of these genetic variants in different populations in order to establish a genetic profile for the disease in specific communities. This study analyzed the APOE polymorphisms regarding susceptibility to AD in a sample of 264 individuals (primarily Caucasians; 82 cases and 182 controls) in the population from Vitória, ES, Brazil, by PCR restriction fragment length polymorphism (PCR-RFLP) methods. The patients were selected according to clinical criteria for probable AD. Whereas the e4 allele showed statistically significant positive association with susceptibility to AD (OR = 3.01, 95%CI = 1.96-4.61; P < 0.0001), the e2 allele did not. The results of the e4 allele confirm the role of this polymorphism as a risk factor for AD in the sample studied as observed in other populations. Although the e3 allele has been considered neutral in several studies, our results suggest that it acts as a protective factor against AD in the population studied (OR = 0.46, 95%CI = 0.30-0.67; P < 0.0001). This study may provide a new insight into the role of the APOE-e3 allele in the etiology of AD and might help to estabilish a profile of risk for AD in the population from Vitória, ES.

Alzheimer's disease (AD) is a complex neurodegenerative disorder and the primary cause of dementia in the elderly and causes a decrease in cognition, functionality, and behaviour. Genetic risk factors play an important role in the pathogenesis of AD. In this case-control study, we aimed to investigate whether single nucleotide polymorphisms in MTHFR (rs1801133), PICALM (3851719), CLU (rs11136000), and CR1 (rs6701713) are associated with AD. Genotype frequencies were evaluated in 82 late-onset AD patients and 161 elderly healthy controls matched by age and gender. We detected a significant association of the MTHFR rs1801133 and PICALM rs3851179 polymorphisms with AD. The results of this study support the hypothesis that several genes are involved in the aetiology of AD.

Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most common type of dementia in the elderly. Although its cause is not completely known, several studies suggest that oxidative stress plays an important role in the etiology of this disease. The SIRT1 and SOD2 proteins are linked to pathways that may impair oxidative stress. In this study, we analyzed the association between polymorphisms in these genes and in the APOE gene, through RT-PCR, as well as between environmental factors and the risk of AD. Additionally, the thiobarbituric acid reactive substance assay was performed to estimate the plasma level of malondialdehyde (MDA), a biomarker of lipid peroxidation. Furthermore, some cytogenetic studies indicate that cells of AD patients show increased chromosomal damage; thus, we performed the micronucleus cytome assay to assess cytogenetic damage in AD patients. As expected, the APOE polymorphisms were found to be highly associated with AD. Additionally, the CT genotype of the SIRT1 gene showed a positive association with the disease. The frequencies of genomic damage (micronucleus, buds, nucleoplasmic bridges and binucleated cells), the presence of cell death biomarkers (condensed chromatin, karyorrhexis and pyknosis), and the plasma level of MDA were significantly greater in AD patients than in controls. Our results support the hypothesis that AD is a condition with increased oxidative stress and genomic instability, which may contribute to the neurodegeneration in AD.

Human longevity is a polygenic and multifactorial trait. Pathways related to lifespan are complex and involve molecular, cellular, and environmental processes. In this analytical observational study, we evaluated the relationship between environment factors, oxidative stress status, DNA integrity level, and the association of FOXO3 (rs2802292), SOD2 (rs4880), APOE (rs429358 and rs7412), and SIRT1 (rs2273773) polymorphisms with longevity in oldest-old individuals from southeastern Brazil. We found an association between the FOXO3 GG genotype and gender. While lifestyle, anthropometric, and biochemical characteristics showed significant results, DNA damage and oxidative stress were not related to lifespan. We found that long-lived individuals with FOXO3 GT genotype had low levels of triglycerides. This study is the first to demonstrate that FOXO3 could be a candidate gene for longevity in the Brazilian population. These results are important in terms of provisions of health care for age-related diseases and lifespan, and provide insight for further research on epigenetic, gene regulation, and expression in oldest-old individuals.