Dataset Information

Plasma microRNA vary in association with the progression of Alzheimer's disease.

ABSTRACT:

Introduction

Early intervention in Alzheimer's disease (AD) requires the development of an easily administered test that is able to identify those at risk. Focusing on microRNA robustly detected in plasma and standardizing the analysis strategy, we sought to identify disease-stage specific biomarkers.

Methods

Using TaqMan microfluidics arrays and a statistical consensus approach, we assessed plasma levels of 185 neurodegeneration-related microRNA, in cohorts of cognitively normal amyloid β-positive (CN-Aβ+), mild cognitive impairment (MCI), and Alzheimer's disease (AD) participants, relative to their respective controls.

Results

Distinct disease stage microRNA biomarkers were identified, shown to predict membership of the groups (area under the curve [AUC] >0.8) and were altered dynamically with AD progression in a longitudinal study. Bioinformatics demonstrated that these microRNA target known AD-related pathways, such as the Phosphoinositide 3-kinase (PI3K-Akt) signalling pathway. Furthermore, a significant correlation was found between miR-27a-3p, miR-27b-3p, and miR-324-5p and amyloid beta load.

Discussion

Our results show that microRNA signatures alter throughout the progression of AD, reflect the underlying disease pathology, and may prove to be useful diagnostic markers.

SUBMITTER: Guevremont D

PROVIDER: S-EPMC8817674 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Plasma microRNA vary in association with the progression of Alzheimer's disease.

Guévremont Diane D Tsui Helen H Knight Robert R Fowler Chris J CJ Masters Colin L CL Martins Ralph N RN Abraham Wickliffe C WC Tate Warren P WP Cutfield Nicholas J NJ Williams Joanna M JM

Alzheimer's & dementia (Amsterdam, Netherlands) 20220205 1

<h4>Introduction</h4>Early intervention in Alzheimer's disease (AD) requires the development of an easily administered test that is able to identify those at risk. Focusing on microRNA robustly detected in plasma and standardizing the analysis strategy, we sought to identify disease-stage specific biomarkers.<h4>Methods</h4>Using TaqMan microfluidics arrays and a statistical consensus approach, we assessed plasma levels of 185 neurodegeneration-related microRNA, in cohorts of cognitively normal ...[more]

PMID: 35141392

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Project description:BackgroundIdentifying biomarkers associated with Alzheimer's disease (AD) progression may enable patient enrichment and improve clinical trial designs. Epigenome-wide association studies have revealed correlations between DNA methylation at cytosine-phosphate-guanine (CpG) sites and AD pathology and diagnosis. Here, we report relationships between peripheral blood DNA methylation profiles measured using Infinium® MethylationEPIC BeadChip and AD progression in participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.ResultsThe rate of cognitive decline from initial DNA sampling visit to subsequent visits was estimated by the slopes of the modified Preclinical Alzheimer Cognitive Composite (mPACC; mPACCdigit and mPACCtrailsB) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) plots using robust linear regression in cognitively normal (CN) participants and patients with mild cognitive impairment (MCI), respectively. In addition, diagnosis conversion status was assessed using a dichotomized endpoint. Two CpG sites were significantly associated with the slope of mPACC in CN participants (P < 5.79 × 10-8 [Bonferroni correction threshold]); cg00386386 was associated with the slope of mPACCdigit, and cg09422696 annotated to RP11-661A12.5 was associated with the slope of CDR-SB. No significant CpG sites associated with diagnosis conversion status were identified. Genes involved in cognition and learning were enriched. A total of 19, 13, and 5 differentially methylated regions (DMRs) associated with the slopes of mPACCtrailsB, mPACCdigit, and CDR-SB, respectively, were identified by both comb-p and DMRcate algorithms; these included DMRs annotated to HOXA4. Furthermore, 5 and 19 DMRs were associated with conversion status in CN and MCI participants, respectively. The most significant DMR was annotated to the AD-associated gene PM20D1 (chr1: 205,818,956 to 205,820,014 [13 probes], Sidak-corrected P = 7.74 × 10-24), which was associated with both the slope of CDR-SB and the MCI conversion status.ConclusionCandidate CpG sites and regions in peripheral blood were identified as associated with the rate of cognitive decline in participants in the ADNI cohort. While we did not identify a single CpG site with sufficient clinical utility to be used by itself due to the observed effect size, a biosignature composed of DNA methylation changes may have utility as a prognostic biomarker for AD progression.

Project description:AimsRecent evidence indicated the biological basis of complement 1q (C1q)/tumor necrosis factor (TNF)-related protein (CTRP) 3, 4, and 14 for affecting brain structure and cognitive function. Thus, we aimed to investigate the association between plasma CTRPs with Alzheimer's disease (AD).MethodsA multicenter, cross-sectional study recruited patients with AD (n = 137) and cognitively normal (CN) controls (n = 140). After the data collection of demographic characteristics, lifestyle risk factors, and medical history, plasma levels of tau phosphorylated at threonine 217 (pT217), pT181, neurofilament light (NfL), CTRP3, 4, and 14 were examined and compared. Multivariate logistic regression analysis was applied to determine associations of plasma CTPRs with the presence of AD. The correlation analysis was used to explore correlations between plasma CTPRs with scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL) scale, and Clinical Dementia Rating Sum of Boxes (CDR-SB), and levels of plasma pT217, pT181, and NfL. Receiver-operating characteristic (ROC) analysis and Delong's test were used to determine the diagnostic power of plasma CTPRs.ResultsPlasma levels of CTRP3, 4, and 14 were higher in AD group than those in CN group. After adjusting for conventional risk factors, CTRP3, CTRP4, and CTRP14 were associated with the presence of AD. In AD patients, CTRP3 was negatively correlated with scores of MMSE and MoCA, while positively correlated with ADL score, CDR-SB score, pT217, and pT181; CTRP4 was positively correlated with CDR-SB score, pT181, and NfL; CTRP14 was negatively correlated with MMSE score, while positively correlated with CDR-SB score, pT217, and NfL. An independent addition of CTRP3 and 4 to the basic model combining age, sex, years of education, APOE4 status, BMI, TG, and HDL-C led to a significant improvement in diagnostic power for AD, respectively.ConclusionsAll the findings preliminarily uncovered associations between plasma CTRPs and AD and suggested the potential of CTRPs as a blood-derived biomarker for AD.

Dataset Information

Plasma microRNA vary in association with the progression of Alzheimer's disease.

Introduction

Methods

Results

Discussion

Publications

Plasma microRNA vary in association with the progression of Alzheimer's disease.

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