Dataset Information

MiRNA-15b and miRNA-125b are associated with regional A?-PET and FDG-PET uptake in cognitively normal individuals with subjective memory complaints.

ABSTRACT: There is substantial experimental evidence for dysregulation of several microRNA (miRNA) expression levels in Alzheimer's disease (AD). MiRNAs modulate critical brain intracellular signaling pathways and are associated with AD core pathophysiological mechanisms. First, we conducted a real-time quantitative PCR-based pilot study to identify a set of brain-enriched miRNAs in a monocentric cohort of cognitively normal individuals with subjective memory complaints, a condition associated with increased risk of AD. Second, we investigated the impact of age, sex, and the Apolipoprotein E ?4 (APOE ?4) allele, on the identified miRNA plasma concentrations. In addition, we explored the cross-sectional and longitudinal association of the miRNAs plasma concentrations with regional brain metabolic uptake using amyloid-? (A?)-positron emission tomography (A?-PET) and ¹⁸F-fluorodeoxyglucose-PET (¹⁸F-FDG-PET). We identified a set of six brain-enriched miRNAs-miRNA-125b, miRNA-146a, miRNA-15b, miRNA-148a, miRNA-26b, and miRNA-100. Age, sex, and APOE ?4 allele were not associated with individual miRNA abundance. MiRNA-15b concentrations were significantly lower in the A?-PET-positive compared to A?-PET-negative individuals. Furthermore, we found a positive effect of the miRNA-15b*time interaction on regional metabolic ¹⁸F-FDG-PET uptake in the left hippocampus. Plasma miRNA-125b concentrations, as well as the miRNA-125b*time interaction (over a 2-year follow-up), were negatively associated with regional A?-PET standard uptake value ratio in the right anterior cingulate cortex. At baseline, we found a significantly negative association between plasma miRNA-125b concentrations and ¹⁸F-FDG-PET uptake in specific brain regions. In an asymptomatic at-risk population for AD, we show significant associations between plasma concentrations of miRNA-125b and miRNA-15b with core neuroimaging biomarkers of AD pathophysiology. Our results, coupled with existing experimental evidence, suggest a potential protective anti-A? effect of miRNA-15b and a biological link between miRNA-125b and A?-independent neurotoxic pathways.

SUBMITTER: Vergallo A

PROVIDER: S-EPMC7840941 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

MiRNA-15b and miRNA-125b are associated with regional Aβ-PET and FDG-PET uptake in cognitively normal individuals with subjective memory complaints.

Vergallo Andrea A Lista Simone S Zhao Yuhai Y Lemercier Pablo P Teipel Stefan J SJ Potier Marie-Claude MC Habert Marie-Odile MO Dubois Bruno B Lukiw Walter J WJ Hampel Harald H

Translational psychiatry 20210127 1

There is substantial experimental evidence for dysregulation of several microRNA (miRNA) expression levels in Alzheimer's disease (AD). MiRNAs modulate critical brain intracellular signaling pathways and are associated with AD core pathophysiological mechanisms. First, we conducted a real-time quantitative PCR-based pilot study to identify a set of brain-enriched miRNAs in a monocentric cohort of cognitively normal individuals with subjective memory complaints, a condition associated with increa ...[more]

PMID: 33504764

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Project description:BACKGROUND:Current methods of amyloid PET interpretation based on the binary classification of global amyloid signal fail to identify early phases of amyloid deposition. A recent analysis of 18F-florbetapir PET data from the Alzheimer's disease Neuroimaging Initiative cohort suggested a hierarchical four-stage model of regional amyloid deposition that resembles neuropathologic estimates and can be used to stage an individual's amyloid burden in vivo. Here, we evaluated the validity of this in vivo amyloid staging model in an independent cohort of older people with subjective memory complaints (SMC). We further examined its potential association with subtle cognitive impairments in this population at elevated risk for Alzheimer's disease (AD). METHODS:The monocentric INSIGHT-preAD cohort includes 318 cognitively intact older individuals with SMC. All individuals underwent 18F-florbetapir PET scanning and extensive neuropsychological testing. We projected the regional amyloid uptake signal into the previously proposed hierarchical staging model of in vivo amyloid progression. We determined the adherence to this model across all cases and tested the association between increasing in vivo amyloid stage and cognitive performance using ANCOVA models. RESULTS:In total, 156 participants (49%) showed evidence of regional amyloid deposition, and all but 2 of these (99%) adhered to the hierarchical regional pattern implied by the in vivo amyloid progression model. According to a conventional binary classification based on global signal (SUVRCereb =?1.10), individuals in stages III and IV were classified as amyloid-positive (except one in stage III), but 99% of individuals in stage I and even 28% of individuals in stage II were classified as amyloid-negative. Neither in vivo amyloid stage nor conventional binary amyloid status was significantly associated with cognitive performance in this preclinical cohort. CONCLUSIONS:The proposed hierarchical staging scheme of PET-evidenced amyloid deposition generalizes well to data from an independent cohort of older people at elevated risk for AD. Future studies will determine the prognostic value of the staging approach for predicting longitudinal cognitive decline in older individuals at increased risk for AD.

Dataset Information

MiRNA-15b and miRNA-125b are associated with regional A?-PET and FDG-PET uptake in cognitively normal individuals with subjective memory complaints.

Publications

MiRNA-15b and miRNA-125b are associated with regional Aβ-PET and FDG-PET uptake in cognitively normal individuals with subjective memory complaints.

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