Beatrice Arosio
University of Milan, Italy
Title: Different rate of progression in elderly Alzheimer’s disease patients: A possible pathophysiological mechanism
Biography
Biography: Beatrice Arosio
Abstract
In late-onset Alzheimer’s disease (AD) the probability of finding other abnormalities in addition to amyloid-beta (Aβ) and tau deposition is increased. The changes induced by aging may be concauses of AD onset and progression. Inflammation, involved in neurodegeneration, can accelerate telomere shortening that reflects cellular turnover and exposure to oxidative and inflammatory damage. IL-10 affects neuronal homeostasis and inhibition of Aβ-induced generation of IL-6, Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IF-γ). After a follow-up period of two years, we have categorized 31 elderly AD as slow (ADS) or fast (ADF) on basis of Mini-Mental State Examination (MMSE) decline (≤3 or ≥5 points, respectively). In peripheral blood mononuclear cells from AD and 20 age-matched controls (HC), we have evaluated IL-10 and IL-6 production after Aβ stimulation, telomere length (TL) and polymorphisms in the promoter of IL-10, IL-6, TNF-α, IF-γ and Transforming Growth Factor-β1. Antigen-specific IL-10 production was higher in ADS and HC after stimulation compared to resting production (40.7±13.7 versus 59.0±27.0; 47.1±25.4 versus 55.3±27.9, respectively; p<0.05) and abrogated in ADF in which prevails AA IFN-γ low-producing genotype (39.7±14.4 versus 42.2±22.4). MMSE decline correlated with TL (R2=0.284; p=0.008) and ADS displayed shorter telomeres compared to ADF and HC (2.0±0.4, 2.5±0.4, 2.3±0.4, respectively; p=0.034). ADF inability to mount anti-inflammatory response to Aβ contributes to deregulation of immune and replicative responses responsible of longer telomeres. These factors might predict the AD progression rate.