The etiology of Alzheimer’s disease is far from being completely understood.Genetic approaches have helped in this matter and have greatly supported the view that theβ-amyloid precursor protein(βAPP)could be at the center of gravity of the pathology.Thus,mutations responsible for autosomal dominant aggressive forms of Alzheimer’s disease(AD)are all harbored by eitherβAPP itself or by its cleaving enzyme presenilins 1/2 referred to asγ-secretase.It was therefore convincing to note that fully independent gene products harboring AD-linked mutations,all concur to modulateβAPP proteolytic processing.These genetic clues combined with a bulk of anatomical observations and cellular manipulations pointed to the role of amyloid-β(Aβ),the main biochemical component of senile plaques that accumulate at late stages of AD.Unfortunately,a series of clinical trials designed to either abolish Aβproduction or neutralize it once produced have consistently failed(Checler et al.,2021).
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