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Current conceptions of the etiology and risk factors for Alzheimer\\\'s disease and their possible implications on the design of dementia clinical trials

Ramit Ravona-Springer, Amos D Korczyn

Many of the clinical trials in Alzheimer’s disease (AD) target the formation, accumulation or clearance of amyloid b (Ab), which is considered to be a pathological hallmark of the disease. These trials have not yet proven efficacy in treatment or prevention of the disease. The failure of these trials may be attributed to a misconception of the role of Ab and the second pathological hallmark of the disease, neurofibrillary tangles, in the most prevalent form of the disease, sporadic AD, compared with the rare early onset, familial AD. In this review, we discuss factors that may affect the results of clinical trials. In addition, the role of several risk factors for AD and their possible interactions with Ab will be reviewed, suggesting a conceptualization of sporadic AD as a heterogenous clinical entity. The implications of such an approach on clinical trials for the treatment and prevention of AD will be discussed.