A Candidate microRNA Profile for Early Diagnosis of Sporadic Alzheimer's Disease

Abstract

Background: Late-onset or sporadic Alzheimer's disease (sAD) is a neurodegenerative disease leading to cognitive impairment and memory loss. The underlying pathological changes take place several years prior to the appearance of the first clinical symptoms, however, the early diagnosis of sAD remains obscure. Objective: To identify changes in circulating microRNA (miR) expression in an effort to detect early biomarkers of underlying sAD pathology. Methods: A set of candidate miRs, earlier detected in biofluids from subjects at early stage of sAD, was linked to the proposed tau-driven adverse outcome pathway for memory loss. The relative expression of the selected miRs in serum of 12 cases (mild cognitive impairment, MCI) and 27 cognitively normal subjects, recruited within the ongoing Aiginition Longitudinal Biomarker Investigation Of Neurodegeneration (ALBION) study, was measured by RT-qPCR. Data on the protein levels of amyloid-β (Aβ42) and total/phosphorylated tau (t-tau/p-tau), in cerebrospinal fluid (CSF), and the cognitive z-scores of the participants were also retrieved. Results: Each doubling in relative expression of 13 miRs in serum changed the odds of either having MCI (versus control), or having pathological Aβ42 or pathological Aβ42 and tau (versus normal) proteins in their CSF, or was associated with the global composite z-score. Conclusion: These candidate human circulating miRs may be of great importance in early diagnosis of sAD. There is an urgent need for confirming these proposed early predictive biomarkers for sAD, contributing not only to societal but also to economic benefits.