Beta‐amyloid pore linked to controlled calcium influx into the cell: A new paradigm for Alzheimer's Disease

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 (Aβ) 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 Aβ‐mediated synaptic plasticity and Aβ trafficking is central for understanding AD pathogenesis and remains a perplexing relationship. The crossover between Aβ pathological and physiological roles is subtle and remains controversial. Based on existing literature, as a signaling molecule, Aβ 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 Aβ pores exert a protective function will unavoidably revolutionize the entire field of anti‐amyloid drug development.