MicroRNA deregulation and chemotaxis and phagocytosis impairment in Alzheimer's disease

Abstract

Introduction: Mononuclear phagocytes play a critical role during Alzheimer’s disease (AD) pathogenesis due to their contribution to innate immune responses and amyloid beta (Ab) clearance mechanisms. Methods: Blood-derived monocytes (BDMs) and monocyte-derived macrophages (MDMs) were isolated from blood of AD, mild cognitive impairment (MCI) patients, and age-matched healthy controls for molecular and phenotypic comparisons. Results: The chemokine/chemokine receptor CCL2/CCR2 axis was impaired in BDMs fromAD and MCI patients, causing a deficit in cell migration. Changes were also observed in MDM-mediated phagocytosis of Ab fibrils, correlating with alterations in the expression and processing of the triggering receptor expressed on myeloid cells 2 (TREM2). Finally, immune-related microRNAs (miRNAs), including miR-155, -154, -200b, -27b, and -128, were found to be differentially expressed in these cells. Discussion: This work provides evidence that chemotaxis and phagocytosis, two crucial innate immune functions, are impaired in AD and MCI patients. Correlations with miRNA levels suggest an epigenetic contribution to systemic immune dysfunction in AD.