Biology subjects

Leite, R.

Publications and source records attributed to Leite, R..

5 recordsLinked to original sources

bioRxiv2026

Is APOE ε2 always a protective allele? Deviations in Hardy-Weinberg equilibrium in admixed Brazilian elderly individuals

The APOE gene is a critical determinant of human healthspan and longevity, with the rare{varepsilon} 2 allele traditionally viewed as a universal protective factor against Alzheimer s disease (AD) and a driver of exceptional lifespan. However, this protective paradigm is predominantly derived from European-centric cohorts, leaving the evolutionary and clinical impacts of{varepsilon} 2 across diverse, highly admixed populations largely unknown due to a lack of local ancestry (LA) resolution. To investigate how local genomic backgrounds modulate APOE survival dynamics we analyzed two Brazilian sample collection of older adults from Sao Paulo city: the Biobank for Aging Studies (BAS, n = 716), a post-mortem autopsy study of naturally deceased individuals; and the Health, Well-being and Aging Study (SABE, n = 952), a census-based elderly sample collection. We evaluated deviations from Hardy-Weinberg equilibrium (HWE) using robust permutation-based models to capture ongoing selective and mortality pressures at the APOE locus. While global APOE frequencies adhered to HWE, integrating LA unveiled striking, mirrored ancestral deviations. Our findings reveal that APOE {varepsilon}2 homozygotes with African ancestry significantly contribute to deviations from HWE in the BAS, with an excess of {varepsilon}2AFR/{varepsilon}2AFR homozygotes observed (p = 0.0196). These distinct HWE deviations demonstrate that an African LA background acts as a genetic buffer, attenuating the phenotypic extreme effects of APOE alleles. Furthermore, we observed an excess of the{varepsilon} 4 European haplotypes in the BAS, which is consistent with a mortality pressure allelic effect in the European LA context. Conversely, the{varepsilon} 4AFR/{varepsilon}4AFR combination was overrepresented in the SABE. While this buffering mechanism mitigates{varepsilon} 4 toxicity, it simultaneously dampens the exceptional longevity advantage typically conferred by the{varepsilon} 2 allele, leading to its neutral accumulation in the post-mortem cohort. Our study challenges the "one-size-fits-all" assumption of APOE biomarkers, demonstrating that{varepsilon} 2 protective mechanisms are context-dependent and modulated by local genomic backgrounds in admixed populations.

genetics↗

bioRxiv2026

Multi-omic profiling of early pregnancy small and large plasma extracellular vesicles reveals placental, metabolic, and structural adaptation signatures

Early human pregnancy is a critical period characterized by rapid growth and extensive maternal-fetal communication that influence maternal and fetal outcomes. Circulating extracellular vesicles (EVs) have the capacity to capture cargo that reflect these processes in real-time; however, signatures of EV subtypes during early pregnancy are poorly defined. Here we quantified mitochondrial DNA (mtDNA) and performed transcriptomic and proteomic profiling of small ([~]100 nm) and large ([~]200 nm) plasma EVs from n=10 normal pregnancies (11-15 weeks) to define subtype-specific molecular signatures. mtDNA and mitochondrial protein content were more abundant in large EVs (lEVs). lEVs also contained a more complex set of long RNAs enriched for placental, immune, and mitochondrial-related transcripts compared with small EVs (sEVs). Proteomic profiling showed enrichment of canonical EV markers and extracellular matrix proteins in sEVs, whereas lEVs were preferentially associated with pregnancy-specific proteins, including proteins related to placental hormone production. MicroRNAs (miRNAs) accounted for [~]25% of small RNAs in both EV subtypes with miR-223 and miR-16 enriched in lEVs and miR-639 enriched in sEVs. These data together, support a model where small and large plasma EVs have distinct, yet complementary signatures reporting systemic adaptations during the critical 11-15 week transition period. This work establishes a foundational framework for future studies linking EV signatures to placental dysfunction and adverse outcomes.

physiology↗

bioRxiv2024

Spatially conserved pathoprotein profiling in the human suprachiasmatic nucleus in progressive Alzheimer disease stages

Individuals with Alzheimers Disease (AD) experience circadian rhythm disorder. The circadian rhythm is synchronized by a master clock, the suprachiasmatic nucleus (SCN), which is a tiny hypothalamic nucleus. Little is known about the molecular and pathological changes that occur in the SCN during AD progression. We examined postmortem brains of 12 controls without AD neuropathological changes (Braak stage 0) and 36 subjects at progressive Braak stages (I, II, and VI). To investigate potential AD-specific changes, we measured the neuronal counts of arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) positive neurons, along with the Braak stages in the SCN. We investigated in adjacent hypothalamic nuclei which are also composed of AVP+ neurons but show more resilience to AD: paraventricular nucleus (PVN) and supraoptic nucleus (SON). To understand the dysregulated proteins associated to AD progression, we performed in-situ proteomics, investigating 57 proteins, including commonly dysregulated in AD, using GeoMx Digital Spatial Profiling (DSP) in the three nuclei (total of 703 area of interests). Neurofibrillary tangles (NFTs) and tau fibrils were found selectively in SCN. We failed to detect NFTs in SON, only a mild dysregulation of p-tau at Braak VI in PVN and SON. Amyloid plaque was absent in the SCN and SON. Additionally, the SCN showed increased glial proteins already at Braak stage I, whereas the level of these proteins sustained in the other nuclei. The SCN is exclusively vulnerable to AD-tau pathology and show immune dysregulation even at Braak I but is protected against amyloid plaque. This finding revealed selectively in amnestic AD, showing more resilience in AD variant. This tau-related molecular dysregulation in the SCN contributes to circadian rhythm disturbances in AD, a phenomenon observed before the onset of cognitive disorder.

neuroscience↗

bioRxiv2024

COVID-19 during pregnancy alters circulating extracellular vesicle cargo and their effects on trophoblast

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and resulting coronavirus disease (COVID-19) causes placental dysfunction, which increases the risk of adverse pregnancy outcomes. While abnormal placental pathology resulting from COVID-19 is common, direct infection of the placenta is rare. This suggests that pathophysiology associated with maternal COVID-19, rather than direct placental infection, is responsible for placental dysfunction and alteration of the placental transcriptome. We hypothesized that maternal circulating extracellular vesicles (EVs), altered by COVID-19 during pregnancy, contribute to placental dysfunction. To examine this hypothesis, we characterized maternal circulating EVs from pregnancies complicated by COVID-19 and tested their effects on trophoblast cell physiology in vitro. We found that the gestational timing of COVID-19 is a major determinant of circulating EV function and cargo. In vitro trophoblast exposure to EVs isolated from patients with an active infection at the time of delivery, but not EVs isolated from Controls, altered key trophoblast functions including hormone production and invasion. Thus, circulating EVs from participants with an active infection, both symptomatic and asymptomatic cases, can disrupt vital trophoblast functions. EV cargo differed between participants with COVID-19 and Controls, which may contribute to the disruption of the placental transcriptome and morphology. Our findings show that COVID-19 can have effects throughout pregnancy on circulating EVs and circulating EVs are likely to participate in placental dysfunction induced by COVID-19.

pathology↗

bioRxiv2019

Chagas disease awareness and socioeconomic characteristics of Bolivian immigrants living in Sao Paulo, Brazil.

In this study, part of a research project on Chagas disease among residents of Bolivia in Sao Paulo, we describe socioeconomic characteristics, knowledge about the disease and access to health services. A structured questionnaire was applied to a sample of 472 Bolivian adults (> 18 years) living in Sao Paulo enrolled in the Barra Funda School Health Center. The median age of participants was 28.5 years, 75.0% from the Bolivian department of La Paz, who were living in Sao Paulo for an average of 5.8 years. Regarding knowledge about the disease and exposure to certain risk factors, 47.7% indicated familiarity with the vector, 23.9% had seen vinchuca in their homes in Bolivia and 6.4% reported having been bitten by a triatomine. The conditions of living in rural areas in Bolivia or in other department than La Paz, have a relative with illness, high school graduation and have seen or been bitten by a vinchuca were significantly associated with the knowledge of the vector. This study provides a view on migration that has important implications for the distribution of Chagas disease and access to health care by providing subsidies for proposing public health policies.\n\nAuthor summaryThis article expresses part of the results of a research project called \"Chagas disease in a population of Bolivian immigrants in Sao Paulo: an analysis of the prevalence of Trypanosoma cruzi infection and morbidity of Chagas disease, knowledge of the population about the disease and access to different levels of health care\". The problem of chronic Chagas disease occurs in many countries, including those not considered endemic, as a result of population movements, mainly by immigration due to urbanization which has led to its globalization. It is now considered an emerging disease with significant potential for transmission via blood transfusions, organ transplants and congenital via, in the absence of appropriate strategies in terms of public health, as well as reactivation of chronic disease in urban centers. Its no different this phenomenon to the city of Sao Paulo. This study analyzed the sociodemographic inserts, labor, migration and knowledge about Chagas disease and its impact on personal, family and professional life of Bolivian immigrants living in Sao Paulo.

scientific communication and education↗