MicroRNA in Alzheimer's disease revisited: implications for major neuropathological mechanisms

Pathology of Alzheimer's disease (AD) goes far beyond neurotoxicity resulting from extracellular deposition of amyloid beta (A beta) plaques. Aberrant cleavage of amyloid precursor protein and accumulation of A beta in the form of the plaque or neurofibrillary tangles are the known primary culprits of AD pathogenesis and target for various regulatory mechanisms. Hyper-phosphorylation of tau, a major component of neurofibrillary tangles, precipitates its aggregation and prevents its clearance. Lipid particles, apolipoproteins and lipoprotein receptors can act in favor or against A beta and tau accumulation by altering neural membrane characteristics or dynamics of transport across the blood-brain barrier. Lipids also alter the oxidative/anti-oxidative milieu of the central nervous system (CNS). Irregular cell cycle regulation, mitochondrial stress and apoptosis, which follow both, are also implicated in AD-related neuronal loss. Dysfunction in synaptic transmission and loss of neural plasticity contribute to AD. Neuroinflammation is a final trail for many of the pathologic mechanisms while playing an active role in initiation of AD pathology. Alterations in the expression of microRNAs (miRNAs) in AD and their relevance to AD pathology have long been a focus of interest. Herein we focused on the precise pathomechanisms of AD in which miRNAs were implicated. We performed literature search through PubMed and Scopus using the search term: ('Alzheimer Disease') OR ('Alzheimer's Disease') AND ('microRNAs' OR 'miRNA' OR 'MiR') to reach for relevant articles. We show how a limited number of common dysregulated pathways and abnormal mechanisms are affected by various types of miRNAs in AD brain.