Role of Amyloid Precursor Protein in Astrocytes in Alzheimer´s Disease.

Abstract

AbstractBackgroundAstrocytes are specialized glial cells that when exposed to inflammatory factors go through a process known as reactive astrogliosis. Reactive astrocytes are a neuropathological feature of Alzheimer’s disease (AD). The etiology of AD is often explained by the accumulation of β‐amyloid peptides, a proteolytic product of the amyloid precursor protein (APP). However, inflammation also plays a prominent role in the development of AD. How reactive astrocytesparticipate in the pathogenesis of AD remains poorly understoodMethodTo elucidate the role of astrocytes in the pathogenesis of AD we exploited different in vitro and in vivo models to investigate the role of Amyloid Precursor protein in setting the immune response of astrocytes.ResultOur results show that overexpression of APP in human cortical astrocytes induces reactive phenotype, similar to astrocytes found in brains of AD patients. These reactive astrocytes produce significantly increased levels of INF‐g in comparison with control astrocytes. Similar positive correlation between APP levels and INF‐g is found also in astrocytes from AD transgenic and traumatic brain injury mice models.ConclusionOur data indicate that astrocytes are activated by high levels of APP, which promotes production and secretion of interferons and recapitulates salient features of astrocytes in AD.