Brain plasticity refers brains ability to change according to physiological and pathological life events.Many different mechanisms participate to brain plasticity, including genesis of new neurons and new synapses, neuron recruitment, re-cycling, and reactivation, neuronal network rewriting.It may produce positive such as negative events.This concept intersects those of brain / cognitive reserve.This latest construct derives from the observation that in the face of neurodegenerative changes that are similar in nature and extent, individuals vary considerably in the severity of the clinical manifestation of that damage.Thus, the extension of brain reserve might affect the age on clinical manifestation of a chronic neurodegenerative disease, or might affect the recovery extension after an acute damage.In turn, brain reserve might be increased by sensory, motor and cognitive stimulation during adult life.In this talk, the possible role of neural progenitors cells (NPC) resident in the mature brain in the functional reserve establishment and maintenance will be discussed also in view of Alzheimer disease.In particular, preclinical data on the possible role of Amyloid Protein Precursor Protein (APP) mutation in NPC regulation will be discussed.The soluble form of APP increases the in vitro proliferation of both fetal and adult neural progenitors.Some indications of the literature also suggest that the products of cleavage of membrane APP, Abeta40 and Abeta42, regulate neurogenesis from primary cultures of neural progenitors.We then studied neural lineage of neurospheres derived from APP-mutated mice, showing that the neurogenic potential is lower both in term of number of newly generated neurons and morphological maturation compared to control animal.In relation to the correlation between hippocampal neurogenesis and performance tests of learning and memory, we studied the hippocampal neurogenesis in 15-months old Tg2576 mice treated with CHF5074 (375 ppm added to the diet), a new modulator of the gamma-secretase from the age of 6 months.Chronic treatment with CHF5074 prevents the greatest decline in the number of age-dependent neuroblasts observed in Tg2576 mice compared to wild-type age-matched (p =0.036).This effect is associated with complete recovery of the defect observed in the context of the memory of Tg2576 mice of 15 months (p =0.006).These data suggest that adult neurogenesis could participate in the brain cognitive reserve, and it might be pharmacologically regulated.