Open AccessAltered Cerebrospinal Fluid Exosomal microRNA Levels in Young-Onset Alzheimer’s Disease and Frontotemporal Dementia
Author(s) -
Yi Jayne Tan,
Benjamin Wong,
Ramanathan Vaidyanathan,
Sivaramapanicker Sreejith,
Sook Yoong Chia,
Nagaendran Kandiah,
Adeline Su Lyn Ng,
Li Zeng
Publication year - 2021
Publication title -
journal of alzheimer's disease reports
Language(s) - English
Resource type - Journals
ISSN - 2542-4823
DOI - 10.3233/adr-210311
Subject(s) - frontotemporal dementia , biomarker , cerebrospinal fluid , microrna , disease , medicine , dementia , microvesicles , alzheimer's disease , fold change , oncology , biology , gene expression , gene , genetics
Background: micro-RNAs (miRNAs) are stable, small, non-coding RNAs enriched in exosomes. Their variation in levels according to different disease etiologies have made them a promising diagnostic biomarker for neurodegenerative diseases such as Alzheimer’s disease (AD). Altered expression of miR-320a, miR-328-3p, and miR-204-5p have been reported in AD and frontotemporal dementia (FTD). Objective: To determine their reliability, we aimed to examine the expression of three exosomal miRNAs isolated from cerebrospinal fluid (CSF) of patients with young-onset AD and FTD (< 65 years), correlating with core AD biomarkers and cognitive scores. Methods: Exosomes were first isolated from CSF samples of 48 subjects (8 controls, 28 AD, and 12 FTD), followed by RNA extraction and quantitative PCR to measure the expression of miR-320a, miR-328-3p, and miR-204-5p. Results: Expression of all three markers (miR-320a (p = 0.005), miR-328-3p (p = 0.049), and miR-204-5p (p = 0.036)) were significantly lower in AD versus controls. miR-320a was reduced in FTD versus controls (p = 0.049) and miR-328-3p was lower in AD versus FTD (p = 0.054). Notably, lower miR-328-3p levels could differentiate AD from FTD and controls with an AUC of 0.702, 95% CI: 0.534– 0.870, and showed significant correlation with lower CSF Aβ42 levels (r = 0.359, p = 0.029). Pathway enrichment analysis identified potential targets of miR-328-3p implicated in the AMPK signaling pathway linked to amyloid-β and tau metabolism in AD. Conclusion: Overall, we demonstrated miR-320a and miR-204-5p as reliable biomarkers for AD and FTD and report miR-328-3p as a novel AD biomarker.