Plasma miRNAs across the Alzheimer's disease continuum: Relationship to central biomarkers

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(11), С. 7698 - 7714

Опубликована: Сен. 18, 2024

Abstract INTRODUCTION MicroRNAs (miRNAs) play important roles in gene expression regulation and Alzheimer's disease (AD) pathogenesis. METHODS We investigated the association between baseline plasma miRNAs central AD biomarkers from Disease Neuroimaging Initiative (ADNI; N = 803): amyloid, tau, neurodegeneration (A/T/N). Differentially expressed their targets were identified, followed by pathway enrichment analysis. Machine learning approaches applied to investigate role of as blood biomarkers. RESULTS identified nine, two, eight significantly associated with A/T/N positivity, respectively. 271 genes targeted amyloid‐related estrogen signaling receptor–mediated among enriched pathways. Additionally, 220 neurodegeneration‐related showed pathways including insulin growth factor 1 pathway. The classification performance demographic information for positivity was increased up 9% inclusion miRNAs. DISCUSSION Plasma biomarkers, highlighting potential Highlights performed analysis microRNAs amyloid/tau/neurodegeneration (A/T/N) biomarker positivity. dysregulated biomarker‐specific/common related improved 9%. Our study highlights

Язык: Английский

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The plasma miRNAome in ADNI: Signatures to aid the detection of at‐risk individuals

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(11), С. 7479 - 7494

Опубликована: Сен. 18, 2024

Abstract INTRODUCTION MicroRNAs are short non‐coding RNAs that control proteostasis at the systems level and emerging as potential prognostic diagnostic biomarkers for Alzheimer's disease (AD). METHODS We performed small RNA sequencing on plasma samples from 847 Disease Neuroimaging Initiative (ADNI) participants. RESULTS identified microRNA signatures correlate with AD diagnoses help predict conversion mild cognitive impairment (MCI) to AD. DISCUSSION Our data demonstrate can be used not only diagnose MCI, but also, critically, MCI Moreover, combined neuropsychological testing, microRNAome evaluation helps conversion. These findings of considerable public interest because they provide a path toward reducing indiscriminate utilization costly invasive testing by defining at‐risk segment aging population. Highlights first analysis ADNI study. The levels several microRNAs prediction Adding in clinical setting increases accuracy prediction.

Язык: Английский

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Circulating small RNAs shed new light on dementia risk

Alzheimer s & Dementia, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

With populations aging worldwide, dementia has an enormous impact on individuals and societies. Alzheimer's disease (AD), the most common form of dementia, is currently estimated to afflict nearly seven million persons over age 65 in United States, a number that could double coming decades.1 Like every disease, quest prevent treat relies discovery biomarkers,2 quantifiable indicators can aid early risk prediction diagnosis. Circulating (peripheral) molecular markers are particularly attractive candidates, given they be easily accessed with minimally invasive procedures, allowing larger-scale applications identify at-risk individuals. Yet critical challenge circulating do not necessarily reflect pathological processes brain, organ plays central role phenotypes. Addressing this challenge, two complementary studies published & Dementia leveraged data from Disease Neuroimaging Initiative (ADNI) suggest promise blood plasma microRNAs (miRNAs) as AD biomarkers. The first study assessed diagnostic potential total 300 miRNAs across 803 age- gender-matched ADNI participants classified controls or having mild cognitive impairment (MCI), late MCI, AD.3 Findings showed composite signature consisting three distinguish diagnoses at baseline further predict longitudinal (12-year) conversion MCI accuracy comparable better than biomarkers clinical screening. second aimed dysregulated association measured participants' cerebrospinal fluid (CSF).4 A 17 unique were found differentially expressed established amyloid (Aβ1-42), tau (total-tau), neurodegeneration (p-tau181) CSF markers. By performing pathway analyses miRNA-targeted genes, several pathways enriched groups Key involved various dementia-related processes, including inflammatory signaling, mitochondria function, cell migration, neuronal projection. Together, these observations support promising underlying biological through which miRNA regulome may contribute risk. Moreover, foregoing have broader implications for research aiming understand promote biomarker discovery. Most dementias thought result complex interplay between genetic environmental factors,5 epigenetic mechanisms heart interplay.6 In particular, provide layer dynamic regulation by influencing levels their target gene transcripts without changing code.7 Intriguingly, disrupt even cross blood-brain barrier under certain conditions,8 indicating act messengers brain pathology detected periphery. similar other modifications contrast mutations, are, principle, preventable reversible,9 makes them potentially modifiable targeted improve outcomes. This possibility been supported preclinical showing interfering select modulates phenotypes.10 prospects line exciting, but future required determine extent serve treatment candidates. First, findings await replication generalization independent cohorts available phenotypes Future work will also need demonstrate utility measurements ability enhance outperform predictive already screening Lastly, additional and, ultimately, needed assess feasibility, safety, efficacy modulating ameliorate author nothing report. declares no conflicts interest.

Язык: Английский

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Preclinical Alzheimer's disease shows alterations in circulating neuronal‐derived extracellular vesicle microRNAs in a multiethnic cohort

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(3)

Опубликована: Март 1, 2025

Alzheimer's disease (AD) is the leading cause of dementia, affecting around 50 million individuals worldwide. Brain-derived extracellular vesicles (EVs) can cross blood-brain barrier carrying neuron-specific molecules, such as microRNAs (miRNAs), which have potential biomarkers neurodegeneration. We explored association between neuronal-derived EV miRNAs from serum and AD clinical status by performing a transcriptome-wide study involving 46 participants with AD, 14 preclinical 60 neurologically healthy controls. identified associated risk, more pronounced transcriptional alterations in compared to individuals. Functional analysis revealed enrichment miRNA-target genes neurodegenerative pathways, highlighting synuclein alpha (SNCA), cytochrome c, somatic (CYCS), microtubule protein tau (MAPT) key targets. Our results highlight role EVs neurodegeneration suggest avenues for further research into brain-derived biomarkers. Neuronal-derived (NDEVs) carry brain tested NDEV (miRNAs) (AD). Fourteen were AD. Preclinical displayed changes than enriched pathways

Язык: Английский

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Opportunities to advance microRNA research in psychiatry

European Neuropsychopharmacology, Год журнала: 2024, Номер 92, С. 26 - 28

Опубликована: Дек. 23, 2024

Язык: Английский

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