Despite the improvements in life expectancy, neurodegenerative diseases (NDGs) havebecome the most dreaded disorders of older people. Aged brains show characteristicchanges that are linked to neurodegeneration raising the question of whether thesehallmarks represent the harbingers of NDGs. Lifestyle factors including, in particularphysical exercise, have given particular attention to factors associated to movementissue as ones of the major factors in modulating the risk of developing NDGs, emphasizingthe interest in the muscle-brain axis. Indeed, one of the crucial systems severelyaffected in several neuromuscular diseases is the loss of effective connection betweenmuscle and nerve, and the neuromuscular junction (NMJ) represents the critical region atthe level of which the two entities communicate.Even if controversy exists on whether pathological events beginning at the NMJ precede orfollow loss of motor units, some recent data highlight as NGDs (e.g. Amyotrophic LateralSclerosis, Alzheimer's Disease, and Parkinson's Disease) and Aging share some commonpathologic features such as the loss of fast-twich fiber, a decreased number of synapticvesicles and sarcopenia giving evidence supports the notion that NMJ dismantlement canoccur independently from motor neuron degeneration and may represent an early pathogenicsignature of muscle-nerve communication defects.The M-Brain project is an observational, analytical case-control study that will apply anew approach to interpret data underling the NMJ dismantlement in NDGs patients bycomparing their clinical and biological information with data obtained from people whohave had a so called "good aging" and those who have had a "bad aging".The study will collect data useful to identify potential predisposing or risk factors forthe subsequent development of a NDGs or able to predict the phenotype traiectories ofselected pathologies with differerent movement levels. The combination of a muscular andneurological phenotyping and a biological characterization combining biomarkers, miRNAand extracellular vesicle (EV) assessments will allow to better identify the determinantsof muscle-brain cross-talk that can then be used as potential indicators for thedefinition of critical morphological and functional components involved in aging and someNGDs. The project then will aim to identify phenotyope trajectories of patients givingparticular attention to the brain-muscle axis and movement issues in order to provideinformation useful for future clinical strategies able to minimaze risk/predisponentFactors.