Peripheral biomarkers to diagnose obstructive sleep apnea in adults: A systematic review and meta-analysis.

BACKGROUND: Obstructive Sleep Apnea (OSA) has been recognized as a major health concern worldwide, given its increasing prevalence, difficulties in diagnosis and treatment, and impact on health, economy, and society. Clinical guidelines highlight the need of biomarkers to guide OSA clinical decision-making, but so far, without success. In this systematic review and meta-analysis, registered on the International Prospective Register of Systematic Reviews database (ID CRD42020132556), we proposed to gather and further explore candidates identified in the literature as potential OSA biomarkers. METHODS: Search strategies for eight different databases (PubMed/Medline, Cochrane Library, Biblioteca Virtual da Saúde, Web of Science, EMBASE, World Intellectual Property Organization database, and bioRxiV and medRxiV Preprint Servers) were developed. We identified studies exploring potential biomarkers of OSA, in peripheral samples of adults, with and without OSA, with no comorbidities defined in study inclusion criteria, published after the last systematic review and meta-analysis conducted on OSA biomarkers, until May 31st, 2020. Risk of bias was assessed through the 14-item Quality Assessment Tool for Diagnostic Accuracy Studies. Demographic, clinical, and candidate biomarkers' data were collected and analyzed via random effects meta-analyses. FINDINGS: Among the 1512 unique studies screened, 120 met the inclusion criteria and 16 studies with low risk of bias were selected for meta-analyses. The selected 16 studies enrolled a total of 2156 participants, from which 1369 were diagnosed with OSA and 787 were disease-free controls. The assessed variables showed high heterogeneity. From the 38 biomarker candidates evaluated, only two were evaluated in more than one study. Most studies pinpointed candidates with more potential for OSA prognosis. ADAM29, FLRT2 and SLC18A3 mRNA levels in PBMCs, Endocan and YKL-40 levels in serum, and IL-6 and Vimentin levels in plasma revealed the most promising candidates for OSA diagnosis. INTERPRETATION: Although the current systematic review and meta-analysis allowed us to identify candidates to further explore as potential biomarkers in future studies, it is evident that OSA biomarkers research is still at an early stage. Most findings derive from small-size single-center study cohorts and single-candidate studies. We point several gaps in current OSA biomarker research that may guide into new directions and approaches towards the identification of OSA biomarkers.

miRNA-31 Improves Cognition and Abolishes Amyloid-ß Pathology by Targeting APP and BACE1 in an Animal Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia worldwide, characterized by progressive memory impairment, behavioral changes, and, ultimately, loss of consciousness and death. Recently, microRNA (miRNA) dysfunction has been associated with increased production and impaired clearance of amyloid-ß (Aß) peptides, whose accumulation is one of the most well-known pathophysiological markers of this disease. In this study, we identified several miRNAs capable of targeting key proteins of the amyloidogenic pathway. The expression of one of these miRNAs, miR-31, previously found to be decreased in AD patients, was able to simultaneously reduce the levels of APP and Bace1 mRNA in the hippocampus of 17-month-old AD triple-transgenic (3xTg-AD) female mice, leading to a significant improvement of memory deficits and a reduction in anxiety and cognitive inflexibility. In addition, lentiviral-mediated miR-31 expression significantly ameliorated AD neuropathology in this model, drastically reducing Aß deposition in both the hippocampus and subiculum. Furthermore, the increase of miR-31 levels was enough to reduce the accumulation of glutamate vesicles in the hippocampus to levels found in non-transgenic age-matched animals. Overall, our results suggest that miR-31-mediated modulation of APP and BACE1 can become a therapeutic option in the treatment of AD.

miRNAs: New Biomarkers and Therapeutic Targets in Dementia.

BACKGROUND: Dementia is a complex pathological state that affects millions of individuals worldwide and is responsible for a huge socioeconomic burden, making it a major health concern of current times. Given the impact of dementia in both patients and caregivers, it is crucial to fully clarify the molecular mechanisms underlying dementia-associated disorders, since without this knowledge our ability to correctly diagnose and treat these diseases is severely hampered. METHODS: Epigenetic mechanisms, such as miRNA-mediated post-transcriptional regulation, have been reported to play a role in dementia pathogenesis. Given their ability to bind complementary mRNA sequences, miRNAs are able to induce temporary or permanent translation repression of their mRNA targets. RESULTS: Consequently, changes in miRNA levels may contribute to alterations in the expression of dementiarelated proteins, impacting the course of the disease. Conversely, studies have also reported that some of these proteins are able to regulate the biogenesis and transport of miRNAs, hinting at novel disease-related mechanisms that are now beginning to be explored. These findings have made miRNAs both interesting tools and promising targets in the design of novel therapeutic strategies. Moreover, the discovery of circulating miRNAs, which are released by cells of various tissues, including the brain, and travel in membrane-bound vesicles found in most biofluids, opened new possibilities concerning the usefulness of miRNAs as biomarkers of disease. CONCLUSION: In this context, the major aim of this review is to discuss the relevance of these small non-coding RNAs in dementia, focusing on their role as gene expression regulators, their potential as biomarkers of dementia subtype and stage, and the hypothesis of using miRNA modulation as an innovative therapeutic approach to treat dementia-related disorders.

Identification of a novel deletion in SURF1 gene: Heterogeneity in Leigh syndrome with COX deficiency.

Leigh syndrome (LS) is a rare, progressive neurodegenerative mitochondrial disorder of infancy. It is a genetically heterogeneous disease. The mutations in SURF1 gene are the most frequently known cause. Here two cases of LS likely caused by SURF1 gene variants are reported: a 39-year-old male patient with a novel homozygous deletion (c.-11_13del), and a case of a 6-year-old boy with the same deletion and a nonsense mutation (c.868dupT), both in heterozygosity. Blue native PAGE showed absence of assembled complex IV. This is the first report of a variant that may abolish the SURF1 gene initiation codon in two LS patients.