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Numerous studies have investigated the risk factors of Alzheimer’s disease (AD), however, AD- risk factors related miRNAs were rarely reported. In this study, AD- risk factor related miRNAs of 119 Chinese individuals (47 AD patients and 62 cognitively normal controls) were investigated. The results showed that education, tea consumption, leisure activity, and social connection were low Body Mass Index (BMI), depression, and smoking were potentially risk factors for AD patients. Moreover, we screened exosome microRNAs (miRNAs) for the aforementioned lifestyle-related factors. Canonical correlation analyses revealed that our clinical observations were correlated with the miRNA expression profile for education, depression, leisure activity, and social connection. Furthermore, we predicted the targets of differentially expressed miRNAs and found that many of them were reported to be involved in the generation and clearance of Amyloid-beta (Aβ), important molecules related to cognition, and disease-activated microglia response to AD. Our results indicated that certain education and depression factors can contribute to AD progression by modulating miRNA expression, implying that preventive interventions might alter AD progression in Chinese patients.

Background Aging is closely associated with the occurrence and development of many complex diseases such as cardiovascular conditions, type 2 diabetes, gastrointestinal (GI) and renal diseases. Detecting changes as early as possible in the human body due to aging is thus crucial significant to potentially mitigate its impacts on physical health. Methods Here, we present a comprehensive metagenome association study and serum metabolomics profiling in a registry Guangxi-Longevity cohort aged from 20–111 years (n=151) and Kunming cohort ages ranging from 20–80 years (n=80). Results We identified uremic toxins as key factors in serum metabolomics highly associated with aging, and this finding has been validated in an independent Kunming-Aging cohort aged from 20–80 years (n=80). We also observed that aging-associated systemic inflammation levels were positively associated with uremic toxins. Moreover, the increased Escherichia coli, Odoribacter splanchnicus, Bilophila wadsworthia and Parabacteroides spp. abundances were related to serum levels of uremic toxins, and the accumulating rate of uremic toxins and specific microbial species was robustly much slower in centenarians than in nonagenarians. We further investigated the frailty and health status in long-living individuals aged above 90 years, and found that the frailty status might be a putative extreme aging phenomenon characterized by novel uremic toxin accumulation patterns. Conclusions Our findings reveal novel potential links between gut microbiota alterations, uremic toxins and aging, and highlight the preponderance of gut microbiota and serum metabolism in aging.

A strong body of evidence supports a role for immune dysregulation across many psychiatric disorders including depression, the leading cause of global disability. Recent progress in the search for genetic variants associated with depression provides the opportunity to strengthen our current understanding of etiological factors contributing to depression and generate novel hypotheses. Here, we provide an overview of the literature demonstrating a role for immune dysregulation in depression, followed by a detailed discussion of the immune-related genes identified by the most recent genome-wide meta-analysis of depression. These genes represent strong evidence-based targets for future basic and translational research which aims to understand the role of the immune system in depression pathology and identify novel points for therapeutic intervention., Highlights • Dysregulated immune function has been strongly linked to depression. • Recent genome-wide association studies support this relationship. • These genes represent strong candidates for etiological and translational research.

Depression is the world's leading cause of disability. Greater understanding of the neurobiological basis of depression is necessary for developing novel treatments with improved efficacy and acceptance. Recently, major advances have been made in the search for genetic variants associated with depression which may help to elucidate etiological mechanisms. The present review has two major objectives. First, we offer a brief review of two major biological systems with strong evidence for involvement in depression pathology: neurotransmitter systems and the stress response. Secondly, we provide a synthesis of the functions of the 269 genes implicated by the most recent genome-wide meta-analysis, supporting the importance of these systems in depression and providing insights into other possible mechanisms involving neurodevelopment, neurogenesis, and neurodegeneration. Our goal is to undertake a broad, preliminary stock-taking of the most recent hypothesis-free findings and examine the weight of the evidence supporting these existing theories and highlighting novel directions. This qualitative review and accompanying gene function table provides a valuable resource and guide for basic and translational researchers, with suggestions for future mechanistic research, leveraging genetics to prioritize studies on the neurobiological processes involved in depression etiology and treatment.