RESUMO
Despite tremendous worldwide efforts, clinical trials assessing Alzheimer's disease (AD)-related therapeutics have been relentlessly unsuccessful. Hence, there is an urgent need to challenge old hypotheses with novel paradigms. An emerging concept is that the amyloid-beta (Aß) peptide, which was until recently deemed a major player in the cause of AD, may instead modulate synaptic plasticity and protect against excitotoxicity. The link between Aß-mediated synaptic plasticity and Aß trafficking is central for understanding AD pathogenesis and remains a perplexing relationship. The crossover between Aß pathological and physiological roles is subtle and remains controversial. Based on existing literature, as a signaling molecule, Aß is proposed to modulate its own turnover and synaptic plasticity through what is currently believed to be the cause of AD: the transient formation of pore-like oligomers. A change of perspective regarding how Aß pores exert a protective function will unavoidably revolutionize the entire field of anti-amyloid drug development.