Impact of Cytokines and Chemokines on Alzheimer's Disease Neuropathological Hallmarks.

Abstract

Background:Alzheimer’s disease (AD) is the most common neurodegenerative disorder, neu-ropathologically characterized by aggregates of β-amyloid peptides, which deposit as senile plaques, and of TAU protein, which forms neurofibrillary tangles. It is now widely accepted that neuroinflammation is implicated in AD pathogenesis.Method:Indeed, inflammatory mediators, such as cytokines and chemokines (chemotactic cytokines) can impact on the Alzheimer´s amyloid precursor protein by affecting its expression levels and amyloidogenic processing and/or β-amyloid aggregation. Additionally, cytokines and chemokines can influence kinases’ activities, leading to abnormal TAU phosphorylation. To date there is no cure for AD, but several thera-peutic strategies have been directed to prevent neuroinflammation. Anti-inflammatory, but also anti-amyloidogenic compounds, such as flavonoids were shown to favourably modulate some pathological events associated with neurodegeneration.Conclusion:This review focuses on the role of cytokines and chemokines in AD-associated pathologies, and summarizes the potential anti-inflammatory therapeutic approaches aimed at preventing or slowing down disease progression.