Fast mimicking diet in Alzheimer’s disease prevention

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder that results in loss of memory and cognitive function, eventually leading to severe dementia. Fasting can be relevant since, recently, studies have shed light on its role in adaptive cellular responses that reduce oxidative damage and inflammation, optimise energy metabolism, and strengthen cellular protection. Fast-mimicking diet (FMD), and re-feeding periods, promote regenerative processes and amelioration of dysfunctional neurons, leading to improvement of symptoms in mice and humans. The wide-range effects of FMDs on metabolic, inflammatory and regenerative pathways have the potential to ameliorate the pathology and symptoms of Alzheimer’s disease (AD). The aim of the project is to investigate the crosstalk between Aβ and Tau that represent a crucial node in the study of the pathogenesis of Alzheimer’s disease related to FMD. Likewise, to explore a new possibility to prevent neurodegeneration in dementia, studying the fast-induced molecular mechanisms that can highlight new pathways and macromolecules involved in the prevention of AD and promote longevity benefit effect. On these bases, we have developed, and behaviorally and histopathological characterised a 5xTg-AD/hTauTg mouse model that mimics the pathological evolution of AD (𝛽-amyloid production /wild type htau expression) to investigate the effect of FMD cycles. We aim to demonstrate that nutrition represents a modifiable environmental factor that could strongly impact AD pathology by modulating its phenotypic expression.