Role of astrocyte aging in the pathogenesis of alzheimer`s disease

Abstract

Alzheimer's disease (AD) is the most abundant severe and irreversible neurodegenerative disease in the world that affects people over 65 years old. The major hallmarks of AD pathology are the senile p-amyloid plaques, hyperphosphorylated neurofibrillary tangles, accompanied by severe neuroinflammation, synaptic disruption, neuronal degeneration and apoptosis, eventually triggering cerebral atrophy, memory loss and cognitive decline. The deposition and increase of p-amyloid levels in the brain induce the cascade of signals triggering production of neurotoxic molecules such as reactive oxygen species, nitric oxide, and proinflammatory cytokines and chemokines that cause neuroinflammation and neurodegeneration eventually resulting into dementia. Aging is the key risk factor for many inflammatory diseases including AD. However, the correlation of aging and AD is poorly investigated. Especially, the cytotoxic effects of p-amyloid in aging glial cells have been poorly explored. Human astrocytes are the most abundant CNS cells that undergo senescence with age and in response to stress. Therefore, it is hypothesized that sensitivity to p-amyloid may significantly change during in vitro senescence of astrocytes. The aim of this study is to investigate the mechanisms of cytotoxic actions of p-amyloid peptide in senescent astrocytes.