Biology subjects

Ludwig, N.

Publications and source records attributed to Ludwig, N..

17 recordsLinked to original sources

bioRxiv2026

Sex-divergent responses to microglial depletion suggest distinct regulatory dependencies in the aged brain

Microglia are essential for brain homeostasis, yet their roles in the aged brain remain poorly defined. Using microRNA (miRNA) profiling, cellular-resolution spatial transcriptomics, and bulk proteomics in 21-month-old mice, we characterize sex-dimorphic responses to microglial depletion via CSF1R inhibition (PLX5622 treatment). Microglia-enriched miRNAs, notably miR-146a-5p and miR-223-3p, were downregulated across different brain regions in both sexes. Transcriptional responses were sex dimorphic: females showed predominantly cell-type-specific downregulation, while males showed bidirectional changes including upregulation of Lzts3, Shank3, and Fgfbp1 alongside downregulation of Ang. Proteomic changes were larger in magnitude and independent from mRNA changes: males exhibited 295 differentially expressed proteins (DEPs) versus 34 in females (8.7-fold difference). Male DEPs had opposing directional shifts in synaptic vesicle proteins (upregulated) and mitochondrial ATP synthesis machinery (downregulated). These data describe sex-dimorphic molecular consequences of microglial loss in the aged brain and identify candidate post-transcriptional mechanisms warranting further investigation.

neuroscience↗

bioRxiv2026

Ex vivo activation unmasks a sex-convergent, exhaustion-associated CD8+ T cell expansion in Parkinsons disease

Parkinsons disease (PD) affects an estimated 6.4 million men and 5.3 million women worldwide, and still lacks a validated peripheral biomarker. Brain tissue is inaccessible in living patients, making peripheral blood an attractive alternative, but existing studies have profiled immune cells almost exclusively as static, resting-state snapshots that cannot reveal how those cells function under challenge. A longitudinal design, following patients over time, or applying a controlled stimulus to reveal functional differences invisible at rest, offers a more sensitive window onto disease-associated dysfunction, and sex, despite differential PD incidence and progression, is rarely treated as a primary variable. Here, using ex vivo PMA/ionomycin stimulation as a controlled functional challenge, we profiled 195k PBMCs from 84 samples of 14 PD patients and 14 controls by single-cell RNA sequencing across an activation time course (0h, 2h, 4h), stratified by sex throughout. Sex explained more transcriptional variance than disease status, and male and female PD patients showed largely divergent responses at rest that converged, by peak activation, on a discrete CD8+ effector memory T cell subpopulation (Tem-CD8). This subpopulation showed an exhaustion-consistent programme, coinciding with a failure to resolve AP-1 induction and a reduction in inferred intercellular communication. The PD peripheral immune phenotype is therefore better characterised as a activation-dependent response than a fixed resting-state signature, identifying Tem-CD8 exhaustion as a disease-associated, sex-convergent candidate for further study.

neuroscience↗

bioRxiv2026

Aging Rhesus Macaque show tissue and sex-specific balance of drifting and coordinated miRNA programs

Macaques research centrality makes it critical to study their molecular aging. We accomplish this for their non-coding transcriptome by sequencing small RNA from 11 organs, with special focus on brain by including 24 brain regions, sampling males and females between ages 3-35 years. Heart, adrenal gland, corpus callosum and caudate putamen showed the most age-deregulated miRNA trajectories. The MIR-154 family, inside the imprinted, rejuvenation-associated Dlk1-Dio3 cluster, was particularly vulnerable. Known age-associated miRNA families LET-7, MIR-29, MIR-17 and MIR-92 were strongly deregulated, with heavy dependence on tissue and sex. MiRNA genomic clusters deregulation was concordant within tissue-sex combinations, implicating upstream regulation rather than random noise. Cross-species comparison with mouse showed ancient miRNAs dominating age-deregulated trajectories. Deregulation direction in tissues-sex was conserved between species at family/cluster levels, but conservation substantially weakened at individual miRNA level. Thus, we mark a decisive step in translating miRNA aging trajectories between two heavily used model organisms. Key FindingsO_LIHeart, adrenal gland, corpus callosum, caudate putamen are hotspots of miRNA age deregulation, with dramatic influence from sex. C_LIO_LINon-brain organs show tissue specific miRNA change, with inconsistent overlap between tissues. C_LIO_LIGenomic clusters of miRNAs were found to be concordant in their age deregulation direction, dependent on tissue and sex, suggesting upstream regulation. C_LIO_LIThe MIR-154 family, housed inside the heavily imprinted Dlk1-Dio3 cluster and processed from the rejuvenation associated MEG3-MIRG host gene is prominently involved in both non-brain organs and brain regions. C_LIO_LIConcentration of age deregulation in evolutionarily ancient miRNAs across species implies regulatory program rather than epigenetic drift, involving MIR-154, LET-7, MIR-29, MIR-17 and MIR-92 families. C_LIO_LIDirection of change conserved between species at the family / genomic cluster level but diminished substantially at individual miRNA level. C_LI

systems biology↗

bioRxiv2026

Physiological re-replication during human stem cell differentiation

During defined developmental windows in Drosophila, controlled re-replication generates physiological gene amplification. Although gene amplification has also been observed during human stem cell differentiation, re-replication in human cells has largely been linked to tumor-associated genome instability. Here, we demonstrate that re-replication likewise operates as a physiological mechanism in human stem cells. Using Rerep-Seq and DNA fiber-combing, we identify distinct phases of re-replication during the differentiation of human myoblasts into myotubes and during the lineage commitment of mesenchymal stem cells toward adipogenic, osteogenic, chondrogenic, and neuronal fates. In all differentiation systems examined, re-replication occurred within defined temporal windows. FACS-isolated re-replicating cells exhibited elevated gene expression using RNA-Seq specifically within re-replicated genomic regions. Moreover, re-replicated DNA was detected as extranuclear DNA. These findings support a model in which cells that do not undergo re-replication, and thus avoid increased chromosomal instability, may nonetheless boost the expression of differentiation-relevant genes by acquiring re-replicated DNA released from neighboring re-replicating cells. We propose that human stem cells exploit an evolutionarily conserved re-replication mechanism to transiently increase gene copy number and thereby meet the heightened protein demands associated with differentiation.

genomics↗

bioRxiv2025

Adenosine-specific transcriptional programs in murine connective tissue type mast cells

Mast cells are tissue-resident immune cells that are critical for the pathogenesis of allergic and inflammatory disorders. In addition to classic host defense against parasites, food quality control through antigen avoidance has been recently elucidated as additional physiological mast cell function. The purine nucleoside adenosine (ADO), like other mast cell activators, such as antigens or Mrgprb2 agonists, increases intracellular Ca2+ concentration; however, it fails to induce degranulation of preformed mediators when applied to isolated mast cells alone, and there is limited knowledge of whether ADO evokes the de novo synthesis and release of inflammatory mediators such as cytokines in tissue mast cells. An unbiased genome-wide analysis of gene expression triggered by various mast cell activators should enable identification of the gene program specifically activated by adenosine in mast cells and thereby reveal new components of the associated inflammatory responses. To this end, we performed bulk RNA sequencing (RNA-Seq) in primary murine peritoneal mast cells (PMCs) as connective tissue mast cells. By comparing responses evoked by ADO stimulation with those of the Mrgprb2 compound 48/80 and antigens that activate Fc{varepsilon}RI receptors, we identified 393 genes whose expression was uniquely regulated by ADO, including upregulation of genes encoding de novo synthesized mediators such as Tgfa and Il7. Transcription factor activity inference, protein classification, functional enrichment analysis, protein-protein interaction network, and topology analysis revealed that these genes play roles in phosphoinositide signaling, vesicle trafficking, glycolysis, mitochondrial activity, and cell cycle arrest. In summary, our work elucidates a distinct ADO-triggered response and identifies a set of proteins including de novo synthesized mediators whose functional relevance in adenosine-evoked mast cell activation and inflammatory reactions can be evaluated in future studies.

pharmacology and toxicology↗

bioRxiv2025

Extracellular vesicles and their RNA cargo facilitate bidirectional cross-kingdom communication between human and bacterial cells

While extracellular vesicles (EVs) are established mediators of intra-species signaling, their role as active participants in cross-kingdom communication remains incompletely understood. Here, we reveal that human colon cells and both Gram-positive and Gram-negative gut bacteria engage in species-specific, EV-mediated molecular dialogue, driven in part by RNA cargo. We show that bacterial EVs (BEVs) induce distinct transcriptomic responses in human cells, and that BEV-RNA independently causes similar effects. Conversely, we demonstrate that human EVs and highly abundant miR-192-5p are differentially internalized by bacteria, affecting their physiology. Our findings support a conceptual model in which EVs function as directional messengers that shape host-microbiome interactions. This study introduces a framework for understanding EVs as cross-kingdom regulators and underscores the importance of tailored, context-specific analyses for understanding the scope of EV-mediated interactions in microbiome-host homeostasis and disease. Highlights[1] L. casei, E. faecalis and P. mirabilis produce BEVs that are internalized by Caco-2 cells at different rates. BEVs produced by L. casei have a positive influence on the viability of Caco-2 cells. Incubation of Caco-2 cells with BEVs leads to changes in the gene expression of immune-response-related genes. [2] BEVs carry RNAs and the type of RNA cargo varies significantly between the BEVs from the different bacteria. Comparison of Caco-2 gene deregulation between BEVs and transfection of RNA isolated from BEV highlights component-specific effects. [3] Caco-2 EVs are taken up by E. faecalis and influence their growth. MiRNA-192-5p can be frequently detected in EVs from Caco-2 cells. Synthetic miR-192-5p is internalized by P. mirabilis and the ability to take up human miRNAs by L. casei and E. faecalis can be increased by packaging of the miRNA in artificial liposomes.

molecular biology↗

bioRxiv2025

Single-cell Spatial Transcriptomics Reveals Disease-specificMicroenvironmental Niches in Neurodegeneration and COVID-19

Neurodegenerative diseases and infections can produce lasting effects on brain function, yet the spatial molecular mechanisms underlying these changes remain poorly understood. Here, we present high-resolution spatial transcriptomics of 40 postmortem brain samples from patients with Parkinsons disease, frontotemporal dementia, dementia with Lewy bodies, and severe COVID-19. Analyzing over 1.5 million spatially resolved cells across dorsolateral prefrontal cortex and anterior cingulate cortex revealed disease-specific transcriptional signatures with pronounced layer-and region-specificity. In Parkinsons disease, we identified stressed neurons creating distinctive microenvironmental gradients where metabolic and protein degradation pathways are elevated near stress epicenters, while regenerative processes increase with distance. COVID-19 brains displayed extensive peripheral immune cell infiltration, particularly in the subcortical white matter, accompanied by compromised blood-brain barrier and coordinated neuroinflammatory responses from microglia, astrocytes, and endothelial cells. Integration of miRNA sequencing with spatial transcriptomics uncovered layer-specific regulatory patterns, including neuroinflammation-associated miR-155. This atlas provides unprecedented insights into disease pathology and highlights the critical importance of spatial molecular context in understanding brain disorders. Key Messages[1] A high-resolution single-cell spatial transcriptomics atlas of the dorsolateral prefrontal cortex and anterior cingulate cortex across neurodegenerative conditions and severe COVID-19 [2] Region-and layer-specific transcriptional dysregulation across disease comparisons reveals disease-specific differential vulnerability [3] Metabolically stressed cells found selectively in the anterior cingulate cortex of Parkinsons disease patients but not in dementia with Lewy bodies, along with detailed characterization of their spatial microenvironment [4] Peripheral immune cell clusters identified in the white matter of the cerebral cortex of COVID-19 patients, with detailed characterization of their spatial microenvironment [5] Integration of bulk miRNA sequencing reveals cortical layer-specific miRNA regulatory patterns

neuroscience↗

bioRxiv2025

A spatio-temporal brain miRNA expression atlas identifies sex-independent age-related microglial driven miR-155-5p increase

An in-depth understanding of the molecular processes composing aging is crucial to develop therapeutic approaches that decrease aging as a key risk factor for cognitive decline. Herein, we present a spatio-temporal brain atlas (15 different regions) of microRNA (miRNA) expression across the mouse lifespan (7 time points) and two aging interventions composed of 1009 samples. MiRNAs are promising therapeutic targets, as they silence genes by complementary base-pair binding of messenger RNAs and are known to mediate aging speed. We first established sex- and brain-region-specific miRNA expression patterns in young adult samples. Then we focused on sex-dependent and independent brain-region-specific miRNA expression changes during aging. The corpus callosum in males and the choroid plexus in females exhibited strong sex-specific age-related signatures. In this work, we identified three sex-independent brain aging miRNAs (miR-146a-5p, miR-155-5p and miR-5100). We showed for miR-155-5p that these expression changes are driven by aging microglia. MiR-155-5p targets mTOR signaling pathway components and other cellular communication pathways and is hence a promising therapeutic target.

molecular biology↗

bioRxiv2024

Spatiotemporal transcriptomic niches of complement pathway and serine protease inhibitor activation in aging and infection

Aging is a multifactorial and complex physiological process, affecting every organ with characteristic manifestations. Understanding the molecular mechanisms that drive aging processes is crucial to targeting age-related disorders. Recent reports suggest that severe post-infection syndromes can partially accelerate aging. However, the underlying gene-encoded regulatory interplay, whether being shared or distinct between aging and infection biology are poorly understood. Here, we employed spatial transcriptomics to establish a multi-organ atlas (brain, heart, kidney, liver, lung, and spleen) across the mouse lifespan (4, 17, and 26 months). Dissecting high-quality fresh-frozen tissue samples at unbiased molecular resolution, we found both organ-specific and cross-organ gene dysregulation upon aging. We identified age-related trajectories in gene expression and cell state, some only detectable within their spatial context, and provide validation at subcellular resolution. The most prominent effect was organ-wide immune system activation with spatially variable severity. We therefore evaluated how aging mimics the expression signatures observed in systemic infection, using spatial transcriptomics slices from young mice infected with Plasmodium berghei ANKA. While on the gene level the effect sizes caused by the infection outweighed those of aging, we reveal a shared activation of the early complement pathway (C4b) and serine protease inhibitors (Serpin gene family) within by phenotype distinct spatial niches. We show that this common RNA signature is driven by tissue-specific cell types and eventually affects protein levels in the aged brain, rendering them a target for future mechanistic and drug discovery studies. Taken together, our study provides a coherent in-depth and cross-organ transcriptomics atlas to systematically study aging and infection in the mouse at spatiotemporal resolution. Key highlightsO_LILarge-scale and high-resolution atlas of spatial transcriptomics from six organs to study aging and systemic infection across two mouse cohorts. C_LIO_LIStrong transcriptional alterations found in distinct organ-specific niches for aging and acute malaria, with organ- and cell type-associated immune responses. C_LIO_LIDysregulation of early complement proteases (C4b) and serine protease inhibitors (Serpina3n) as common theme across central nervous system and peripheral organs. C_LI

molecular biology↗

bioRxiv2024

Quantitative design of cell type-specific mRNA stability from microRNA expression data

Limiting expression to target cell types or states is a longstanding goal in gene therapy, which could be met by sensing endogenous microRNA. However, an unclear association between microRNA expression and activity currently hampers such an approach. Here, we probe this relationship by measuring the stability of synthetic microRNA-responsive 3UTRs across 10 cell lines in a library format. By systematically addressing biases in microRNA expression data and confounding factors such as microRNA crosstalk, we demonstrate that a straightforward model can quantitatively predict the stability of reporters containing full microRNA target sites purely from expression data. We use this model to design constructs with previously unattainable response patterns across our cell lines. We then generalize this approach to primary tissues and cells and show that mRNA can be engineered to be differentially active between rested and exhausted T cell states. The rules we derive for microRNA expression data selection and processing should apply to microRNA-responsive devices for any environment with available expression data.

synthetic biology↗

bioRxiv2023

Th17 cells target the metabolic miR-142-5p-SDHC/SDHD axis promoting invasiveness and progression of cervical cancers

During cervical carcinogenesis, T-helper (Th)-17 cells accumulate in the peripheral blood and tumor tissues of cancer patients. We previously demonstrated that Th17 cells are associated with therapy resistance as well as cervical cancer metastases and relapse, however, the underlying Th17-driven mechanisms supporting cervical cancer progression are not fully understood as yet. In this study, we found that Th17 cells promote migration and invasion of cervical cancer cells in 2D cultures and 3D spheroids. We demonstrated that Th17 cells induced the expression of miR-142-5p in cervical cancer cells supporting their migration and invasiveness. As the responsible mechanism, we identified the subunits C and D of the succinate dehydrogenase (SDH) complex as new targets of miR-142-5p and provided evidence that Th17 cells reduced the expression of SDHC and SDHD that was dependent on miR-142-5p. Functional downstream analysis with inhibitors of miR-142-5p and siRNA knock down of SDHC and SDHD revealed that Th17-induced miR-142-5p-mediated reduced expression of SDHC and SDHD was responsible for enhanced migration and invasion of cervical cancer cells. Consistently, cervical cancer patients exhibited high levels of succinate in their serum associated with lymph node metastases and diminished expression of SDHD in patients' biopsies significantly correlated with increased numbers of Th17 cells, advanced tumor stage and lymph node metastases. Correspondingly, a combination of weak or negative SDHD expression and a ratio of Th17/CD4+ T cells > 43.90 % in situ was associated with reduced recurrence free survival. In summary, we unraveled a novel molecular mechanism by which Th17 cells promote cervical cancer progression and suggest evaluation of Th17 cells as a potential target for immunotherapy in cervical cancer.

cancer biology↗

bioRxiv2021

Vesicle-bound regulatory RNAs are associated with tissue aging

Previous work on murine models and human demonstrated global as well as tissue-specific molecular aging trajectories in solid tissues and body fluids1-8. Extracellular vesicles like exosomes play a crucial role in communication and information exchange in between such systemic factors and solid tissues9,10. We sequenced freely circulating and vesicle-bound small regulatory RNAs in mice at five time points across the average life span from 2 to 18 months. Intriguingly, each small RNA class exhibits unique aging patterns, which showed differential signatures between vesicle-bound and freely circulating molecules. In particular, tRNA fragments showed overall highest correlation with aging which also matched well between sample types, facilitating age prediction with non-negative matrix factorization (86% accuracy). Interestingly, rRNAs exhibited inverse correlation trajectories between vesicles and plasma while vesicle-bound microRNAs (miRNAs) were exceptionally strong associated with aging. Affected miRNAs regulate the inflammatory response and transcriptional processes, and adipose tissues show considerable effects in associated gene regulatory modules. Finally, nanoparticle tracking and electron microscopy suggest a shift from overall many small to fewer but larger vesicles in aged plasma, potentially contributing to systemic aging trajectories and affecting the molecular aging of organs.

molecular biology↗

bioRxiv2021

Suppression of endothelial miR-22-3p mediates non-small cell lung cancer cell-induced angiogenesis

MicroRNAs (miRNAs) expressed in endothelial cells (ECs) are powerful regulators of angiogenesis, which is essential for tumor growth and metastasis. Here, we demonstrated that miR-22-3p (miR-22) is preferentially and highly expressed in ECs, while its endothelial level is significantly down-regulated in human non-small cell lung cancer (NSCLC) tissues when compared to matched non-tumor lung tissues. This reduction of endothelial miR-22 is induced by NSCLC cell-secreted tumor necrosis factor (TNF)- and interleukin (IL)-1{beta}. Endothelial miR-22 functions as a potent angiogenesis inhibitor that inhibits all the key angiogenic activities of ECs and consequently NSCLC growth through directly targeting sirtuin (SIRT) 1 and fibroblast growth factor receptor (FGFR) 1 in ECs, leading to inactivation of AKT/mammalian target of rapamycin (mTOR) signaling. These novel findings provide insight into the molecular mechanisms of NSCLC angiogenesis and indicate that endothelial miR-22 represents a potential target for the future anti-angiogenic treatment of NSCLC.

cancer biology↗

bioRxiv2020

Broad transcriptional dysregulation of brain and choroid plexus cell types with COVID-19

Though SARS-CoV-2 primarily targets the respiratory system, it is increasingly appreciated that patients may suffer neurological symptoms of varied severity1-3. However, an unbiased understanding of the molecular processes across brain cell types that could contribute to these symptoms in COVID-19 patients is still missing. Here, we profile 47,678 droplet-based single-nucleus transcriptomes from the frontal cortex and choroid plexus across 10 non-viral, 4 COVID-19, and 1 influenza patient. We complement transcriptomic data with immunohistochemical staining for the presence of SARS-CoV-2. We find that all major cortex parenchymal and choroid plexus cell types are affected transcriptionally with COVID-19. This arises, in part, from SARS-CoV-2 infection of the cortical brain vasculature, meninges, and choroid plexus, stimulating increased inflammatory signaling into the brain. In parallel, peripheral immune cells infiltrate the brain, microglia activate programs mediating the phagocytosis of live neurons, and astrocytes dysregulate genes involved in neurotransmitter homeostasis. Among neurons, layer 2/3 excitatory neurons--evolutionarily expanded in humans4--show a specific downregulation of genes encoding major SNARE and synaptic vesicle components, predicting compromised synaptic transmission. These perturbations are not observed in terminal influenza. Many COVID-19 gene expression changes are shared with those in chronic brain disorders and reside in genetic variants associated with cognitive function, schizophrenia, and depression. Our findings and public dataset provide a molecular framework and new opportunities to understand COVID-19 related neurological disease.

neuroscience↗

bioRxiv2020

Competitive learning suggests circulating miRNA profiles for cancers decades prior to diagnosis

Small non-coding RNAs such as microRNAs are master regulators of gene expression. One of the most promising applications of miRNAs is the use as liquid biopsy. Especially early diagnosis is an effective means to increase patients overall survival. E.g. in oncology a tumor is detected at best prior to its clinical manifestation. We generated genome-wide miRNA profiles from serum of patients and controls from the population-based Janus Serum Bank (JSB) and analyzed them by bioinformatics and artificial intelligence approaches. JSB contains sera from 318,628 originally healthy persons, more than 96,000 of whom later developed cancer. We selected 210 serum samples of patients with lung, colon or breast cancer at three time points prior to diagnosis, after cancer diagnosis and controls. The controls were matched with regard to age of the blood donor and to the time points of blood drawing, which were 27, 32, or 38 years prior to diagnosis. Using ANOVA we report 70 significantly deregulated markers (adjusted p-value<0.05). The driver for the significance was the diagnostic time point (miR-575, miR-6821-5p, miR-630 had adjusted p-values<10-10). Further, 91miRNAs were differently expressed in pre-diagnostic samples as compared to controls (nominal p<0.05). Unsupervised competitive learning by self-organized maps indicated larges effects in lung cancer samples while breast cancer samples showed the least pronounced changes. Self-organized maps also highlighted cancer and time point specific miRNA dys-regulation. Intriguingly, a detailed breakdown of the results highlighted that 51% of all miRNAs were highly specific, either for a time-point or a cancer entity. Our results indicate that tumors may be indicated by serum miRNAs decades prior the clinical manifestation.

cancer biology↗

bioRxiv2019

Systematic assessment of blood-borne microRNAs highlights molecular profiles of endurance sport and carbohydrate uptake

Multiple studies endorsed the positive effect of regular exercising on mental and physical health. However, the molecular mechanisms underlying training-induced fitness in combination with personal life-style remain largely unexplored. Circulating biomarkers such as microRNAs (miRNAs) offer themselves for studying systemic and cellular changes since they can be collected from the bloodstream in a low-invasive manner. In Homo sapiens miRNAs are known to regulate a substantial number of protein-coding genes in a post-transcriptional manner and hence are of great interest to understand differential gene expression profiles, offering a cost-effective mechanism to study molecular training adaption, and connecting the dots from genomics to observed phenotypes.\n\nHere, we investigated molecular expression patterns of 2, 549 miRNAs in whole-blood samples from 23 healthy and untrained adult participants of a cross-over study, consisting of 8 weeks of endurance training, with several sessions per week, followed by 8 weeks of washout and another 8 weeks of running, using microarrays. Participants were randomly assigned to one of the two study groups, one of which administered carbohydrates before each session in the first training period, switching the treatment group for the second training period. During running sessions clinical parameters as heartbeat frequency were recorded. This information was extended with four measurements of maximum oxygen uptake (VO2 max) for each participant.\n\nWe observed that multiple circulating miRNAs show expression changes after endurance training, leveraging the capability to separate the blood samples by training status. To this end, we demon-strate that most of the variance in miRNA expression can be explained by both common and known biological and technical factors. Our findings highlight six distinct clusters of miRNAs, each exhibiting an oscillating expression profile across the four study timepoints, that can effectively be utilized to predict phenotypic VO2 max levels. In addition, we identified miR-532-5p as a candidate marker to determine personal alterations in physical training performance on a case-by-case analysis taking the influence of a carbohydrate-rich nutrition into account. In literature, miR-532-5p is known as a common down-regulated miRNA in diabetes and obesity, possibly providing a molecular link between cellular homeostasis, personal fitness levels, and health in aging.\n\nWe conclude that circulating miRNAs expression can be altered due to regular endurance training, independent of the carbohydrate availability in the timeframe around training. Further validation studies are required to confirm the role of exercise-affected miRNAs and the extraordinary function of miR-532-5p in modulating the metabolic response to a high availability of glucose.

systems biology↗

bioRxiv2019

Machine learning to detect Alzheimer’s disease from circulating non-coding RNAs

BackgroundTo develop therapeutics for Alzheimers disease, early detection of patients awakes new hope. Circulating small non-coding RNAs are among the prominent candidates for a blood-based diagnosis, requiring however growing cohort sizes.\n\nMethodsWe determined abundance levels of 21 known circulating microRNAs in 465 individuals encompassing Alzheimers patients and controls recruited in US and Germany. We computed models to assess the relation between microRNA-expression and phenotypes, gender, age and disease severity (Mini-Mental State Examination MMSE).\n\nResults20 of 21 miRNAs were consistently dys-regulated in the US and Germany. 18 were significantly correlated to neurodegeneration (adjusted p<0.05) with highest significance for miR-532-5p (adjusted p=4.8x10-30). Ten miRNAs were significantly correlated with MMSE, in particular miR-26a/26b-5p (adjusted p=0.0002). Machine learning models reached an AUC value of 87.6% in differentiating AD patients from controls.\n\nConclusionsOur data provide strong evidence for the relevance of circulating non-coding RNAs to detect Alzheimers from a blood sample.

bioinformatics↗