The drug discovery for disease-modifying agents in Alzheimer disease (AD) is facing a failure of clinical trials
with drugs based on two driving hypotheses, i.e. the cholinergic and amyloidogenic hypotheses. In this article we recapitulate
the main aspects of AD pathology, focusing on possible mechanisms for synaptic dysfunction, neurodegeneration
and inflammation. We then present the pharmacological and neurobiological profile of a novel compound (CHF5074)
showing both anti-inflammatory and gamma-secretase modulatory activities, discussing the possible time-window for effective
treatment in an AD transgenic mouse model. Finally, the concept of cognitive reserve is introduced as possible
target for preventive therapies.
Keywords: Tg2576, amyloid precursor protein, cognitive reserve, neuroinflammation, translational medicine.
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