Background: There is an urgent need for noninvasive, cost-effective biomarkers for Alzheimer's disease (AD), such as blood-based biomarkers. They will not only support the clinical diagnosis of dementia but also allow for timely pharmacological and nonpharmacological interventions and evaluations.
Objective: To identify and validate a novel blood-based microRNA biomarker for dementia of the Alzheimer's type (DAT).
Methods: We conducted microRNA sequencing using peripheral blood mononuclear cells isolated from a discovery cohort and validated the identified miRNAs in an independent cohort and AD postmortem tissues. miRNA correlations with AD pathology and AD clinical-radiological imaging were conducted. We also performed bioinformatics and cell-based assay to identify miRNA target genes.
Results: We found that miR-150-5p expression was significantly upregulated in DAT compared to mild cognitive impairment and healthy subjects. Upregulation of miR-150-5p was observed in AD hippocampus. We further found that higher miR-150-5p levels were correlated with the clinical measures of DAT, including lower global cognitive scores, lower CSF Aβ42, and higher CSF total tau. Interestingly, we observed that higher miR-150-5p levels were associated with MRI brain volumes within the default mode and executive control networks, two key networks implicated in AD. Furthermore, pathway analysis identified the targets of miR-150-5p to be enriched in the Wnt signaling pathway, including programmed cell death 4 (PDCD4). We found that PDCD4 was downregulated in DAT blood and was downregulated by miR-150-5p at both the transcriptional and protein levelsConclusion:Our findings demonstrated that miR-150-5p is a promising clinical blood-based biomarker for DAT.
Keywords: Alzheimer’s dementia; MRI; biomarker; cerebrospinal fluid; microRNA.