Amerindian genetic ancestry protects against Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia worldwide, and bears remarkable evidence for a differential prevalence among continental populations. In this scenario, estimating ancestry proportions in recently admixed populations is a strategy that can help increasing knowledge about the genetic structure of this complex trait. AIM/METHODS: Our purpose was to assess mean ancestry estimates for the three main parental contributors to the Brazilian contingent (European, African and Amerindian) using a panel of 12 ancestry informative markers. Outpatients with the late-onset form of AD (n = 120) were compared for ancestry levels with non-cognitively impaired subjects (n = 412) in the Midwest Brazil, controlling for classic clinical, social and anthropometric risk factors. RESULTS: Our findings show a 3-fold greater genetic Amerindian content among control subjects compared to AD patients (p < 0.001). CONCLUSION: Our results suggest that the allelic architecture of Native Americans can confer protection against the onset of the disease.

Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer's disease.

BACKGROUND: MicroRNAs (miRNAs) emerged as regulatory elements, with up to 70 % of all miRNAs found in the brain, playing key roles in the onset of Alzheimer's disease (AD). OBJECTIVE: to broadly assess the expression levels of miRNAs in post-mortem brain (PMB) samples of individuals deceased with or without AD. METHODS: A high-throughput microarray platform was used to sketch miRNA samples isolated from superior and middle temporal gyrus of A+T+ AD cases, compared to samples from age- and sex-matched AD-devoid donors, all pulled from the University of São Paulo's Brain Biobank. The miRNAs identified by microarray were subjected to validation with specific qRT-PCR assays employing independent PMB samples. RESULTS: The analyses yielded 6 miRNAs differentially expressed (miR-30e_3p; miR-365b_5p; miR-664_3p; miR-1202; miR-4286; miR-4449), and their interplay with specific AD-related genes and signaling pathways was explored using bioinformatics analyses (including the KEGG package, mirPath v.3). In the end, 3 miRNAs, 7 target genes and 11 pathways were found closely interrelated and implicated with the AD pathophysiology. CONCLUSION: A dysregulation on a subset of these miRNAs appear to affect a range of genes (notably PTEN) and pathways (emphasis to PI3K-AKT) so to provide grounds for neuronal death by apoptotic signaling, autophagy and/or oxidative damage.

Evidence for a contribution of the APOE (but not the ACE) gene to the sleep profile of non-demented elderly adults.

This study aims to investigate alleles of the human apolipoprotein E (APOE) and of the angiotensin-converting enzyme (ACE) genes as risk factors for poor quality of sleep in elderly individuals with no major cognitive decline. This cross-sectional, analytical study was conducted with 163 participants aged 75 years in average and 85% female. Sociodemographic, anthropometric and clinical data were gathered, and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth scale, with patient followed for years prior to these evaluations to rule out onset of major mental disorders. Genotyping of classic polymorphic sites for the ApoE (rs429358 and rs7412) and the ACE (rs4646994) genes used peripheral DNA. A total of 63% of the subjects reported poor quality of sleep assessed by the PSQI whereas 54 (33%) reported daytime sleepiness through the Epworth scale. A significant correlation was observed between APOE and PSQI, with a greater frequency of the poor nighttime sleep quality phenotype among ε2 carriers, whereas no correlation was found among any of the sleep scores and the ACE genotypes. Thus, we suggest a correlation between APOE alleles and scale-assessed sleep quality scores in older adults, with no implications for ACE alleles, in a context devoid of cognitive impairment.

Interplay between circulating nitric oxide and interleukin-17 in elderly outpatients with non-inflammatory conditions.

Nitric oxide (NOx) availability in biological systems is associated with either favorable or unfavorable outcomes. In this sense, several studies bring about evidence that unbalanced NOx production may be underlying to the pathophysiology of vascular disorders. Our study investigated the possible association of clinical, biochemical and inflammatory variables with total circulating levels of NOx in elderly patients devoid of major inflammatory conditions. Clinical (demographics, lifestyle, anthropometry, pressoric traits) and biochemical characteristics (lipemic, glycemic and hormonal profiles) were assessed from 168 geriatrics outpatients eligible for primary care for age-related disorders. Furthermore, circulating levels of 10 inflammatory mediators and of NOx were measured. Correlation tests analyzed categorical or continuous traits according to serum NOx and found no association between NOx and any of the clinical or laboratory data but a negative correlation between plasma NOx concentrations and levels of the immune mediator IL17a (r = -0.236; P = 0.004). Evidence for a correlation between circulating NOx and IL17 is already present in the literature, mostly from studies conducted under inflammatory conditions. Our hypothesis is that such negative correlation can be attributed to an endogenous homeostatic system that IL17 production by the constitutively produced NOx from the vascular endothelium.

Apoliprotein E genotype is associated with apoliprotein B plasma levels but not with coronary calcium score in very elderly individuals in primary care setting.

BACKGROUND: Epidemiological surveys indicate the influence of polymorphisms of apolipoprotein (apo) E on plasma lipids and triglyceride-rich lipoprotein levels, with impact on atherosclerotic phenotypes. AIM: We studied the association of classic genotypes of the apoE gene with clinical and biochemical risk factors for atherosclerosis in a segment of the very-old Brazilian individuals, with emphasis on the lipemic profile. METHODS: We performed cross-sectional analyses of clinical and laboratory assessments, including cardiac computed tomography, across ε2, ε3 and ε4 carriers of the apoE gene with a convenience sample of 208 participants eligible for prevention against cardiovascular events. RESULTS: When non-ε4 carriers were compared with ε4 carrying subjects, lower levels of ApoB as well as ApoB/ApoA ratios were observed in the former group. Tests between apoE polymorphisms with other clinical/biochemical variables and those with arterial calcification showed no significant differences between groups. CONCLUSION: The study suggests a possible atherogenic role of the ε4 allele attributable to increased ApoB levels and ApoB/ApoA ratios among very-old subjects in primary care setting.