Inflammation, genes and zinc in Alzheimer's disease

Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disease which in Western society mainly accounts for clinical dementia, AD has been linked to inflammation and metal biological pathway. Neuro-pathological hallmarks are senile plaques, resulting from the accumulation of several proteins and an inflammatory reaction around deposits of amyloid, a fibrillar protein, A beta, product of cleavage of a much larger protein, the beta-amyloid precursor protein (APP) and neurofibrillary tangles. Amyloid deposition, due to the accumulation of A beta peptide, is the main pathogenetic mechanism. Inflammation clearly occurs in pathologically vulnerable regions of AD and several inflammatory factors influencing AD development, i.e. environmental factors (pro-inflammatory phenotype) and/or genetic factors (pro-inflammatory genotype) have been described. At the biochemical level metals such as zinc are known to accelerate the aggregation of the amyloid peptide and play a role in the control of inflammatory responses. in particular, zinc availability may regulate mRNA cytokine expression, so influencing inflammatory network phenotypic expression. (C) 2007 Elsevier B.V. All rights reserved.