microRNA-Based Biomarkers in Alzheimer’s Disease (AD)

Alzheimer’s disease (AD) is a multifactorial, age-related neurological disease characterized by complex pathophysiological dynamics taking place at multiple biological levels, including molecular, genetic, epigenetic, cellular and large-scale brain networks. These alterations account for multiple pathophysiological mechanisms such as brain protein accumulation, neuroinflammatory/neuro-immune processes, synaptic dysfunction, and neurodegeneration that eventually lead to cognitive and behavioral decline. Alterations in microRNA (miRNA) signaling have been implicated in the epigenetics and molecular genetics of all neurobiological processes associated with AD pathophysiology. These changes encompass altered miRNA abundance, speciation and complexity in anatomical regions of the CNS targeted by the disease, including modified miRNA expression patterns in brain tissues, the systemic circulation, the extracellular fluid (ECF) and the cerebrospinal fluid (CSF). miRNAs have been investigated as candidate biomarkers for AD diagnosis, disease prediction, prognosis and therapeutic purposes because of their involvement in multiple brain signaling pathways in both health and disease. In this review we will: (i) highlight the significantly heterogeneous nature of miRNA expression and complexity in AD tissues and biofluids; (ii) address how information may be extracted from these data to be used as a diagnostic, prognostic and/or screening tools across the entire continuum of AD, from the preclinical stage, through the prodromal, i.e., mild cognitive impairment (MCI) phase all the way to clinically overt dementia; and (iii) consider how specific miRNA expression patterns could be categorized using miRNA reporters that span AD pathophysiological initiation and disease progression.