The observed findings suggest that investigated miRNAs are not suitable for differentiation between different stages of cognitive impairment, however, miRNAs were associated with typical hallmarks of AD, which supports their important role in neurodegeneration.
Abstract
Epigenetic changes can affect Alzheimer's disease (AD) susceptibility. miRNAs are novel potential circulating biomarkers of AD and mild cognitive impairment (MCI) that could support cerebrospinal fluid (CSF) biomarkers in earlier diagnosis of the disease or determination of disease stage. Our aim was to assess differences in expression of target miRNAs in patients with different stages of cognitive impairment and to evaluate the association with CSF biomarkers or cognitive test score (MMSE). We included 117 patients with cognitive impairment, among them 62 AD patients, 24 MCI patients with pathological CSF biomarker levels, and 31 MCI patients with normal CSF biomarker levels. Expression of seven target miRNAs was measured in patients' blood plasma, CSF and extracellular vesicles (EVs) enriched from plasma and CSF. None of the investigated miRNAs were differentially expressed between AD and MCI groups. Four miRNAs were associated with CSF biomarker levels, both in plasma (hsa-miR-375-3p) and CSF (hsa-miR-146a-5p, hsa-miR-29c, hsa-miR-107). The observed findings suggest that investigated miRNAs are not suitable for differentiation between different stages of cognitive impairment. However, miRNAs were associated with typical hallmarks of AD, which supports their important role in neurodegeneration. Therefore, miRNA regulatory networks could contribute to better understanding of the biological processes involved in cognitive impairment.
The findings identify a group of peripheral inflammatory markers associated with AD pathology and suggest that some of these relationships may vary by sex, warranting larger studies to clarify the role of sex in AD pathobiology.
R. Coig, L. Jain, M. Khrestian et al.· medRxiv· 0 citations
Among patients with isolated AD or isolated CSVD, plasma p-Tau217 is the optimal specific biomarker for the diagnosis of AD and differentiation between AD and cerebral small vessel disease.
Xian-dong Wang, Junchi Wu, Xuan Zhang et al.· Frontiers in Neurology· 0 citations
BackgroundDifferential expression of long non-coding RNAs (lncRNAs) in brain, serum, and blood show strong potential to distinguish Alzheimer's disease (AD) from healthy controls.ObjectiveTo explore whether lncRNA signatures delineate AD pathology and map to distinct, multidimensional cognitive domains, enhancing specificity in assessing AD severity and progression.MethodsWe profiled 29,603 lncRNAs transcripts in blood samples from 15 AD patients and 15 healthy controls, alongside comprehensive neuropsychological assessments. Generalized Linear Models and Predictive Power Score analyses, with statistical prioritization, identified lncRNAs associated to AD neuropsychological architecture.ResultsSeveral lncRNAs share strongly associated with cognitive performance and AD severity, mapping to genes involved in key AD-related molecular processes, including synaptic and neurotransmitter regulation (e.g., EPHB1, CHRNA4, TEAD1), protein homeostasis and Aβ pathology (e.g., FBXL2, FAM221A, APP), mitochondrial function and cellular stress (e.g., VDAC3, PPT2-EGFL8), neuroinflammation and immune regulation (e.g., TEAD1, EMX2OS, LY6E-DT), epigenetic and transcriptional control (e.g., PRDM2, DLEU1, FIRRE), neuronal excitability (e.g., KCNJ14), and neuroprotection and synaptic plasticity (e.g., SIL1). Novel associations included ferroptosis, DNA stability, microtubule dynamics, and dendritic orientation (e.g., BTB3, DICER1, GNG7, IBA57, NEAT1, POT1, SRD5A3).ConclusionsWe identify candidate lncRNA signatures that may serve as potential biomarkers and enhance our understanding of the molecular basis of the cognitive architecture in AD, opening new avenues for biomarker identification and targeted therapeutic strategies development. Validation in larger, diverse cohorts is essential to confirm their mechanistic contributions to AD.
M. I. Mosquera-Heredia, Oscar M Vidal, E. Barceló et al.· Journal of Alzheimer's Disea...· 0 citations
These findings highlight the complementary roles of CSF and plasma tau biomarkers in tracking disease progression: CSF biomarkers capture early pathological changes, whereas plasma biomarkers more effectively reflect disease progression within symptomatic stages.
J. Arranz, J. Lantero-Rodríguez, Luisa Sophie Braun-Wohlfahrt et al.· EBioMedicine· 1 citation
Increased serum p-tau217 and decreased ApoE levels were significantly associated with greater AD severity, suggesting that both biomarkers may serve as complementary noninvasive indicators of disease severity in Alzheimer’s disease.
Ahmed Kadom Kalaf, Khawla A. Shemran, Waleed Azeez AlAmeedy· International Journal of Nut...· 0 citations
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