Modulation of gamma- and beta-Secretases as Early Prevention Against Alzheimer's Disease

The genetic evidence implicating amyloid-beta in the initial stage of Alzheimer's disease is unequivocal. However, the long biochemical and cellular prodromal phases of the disease suggest that dementia is the result of a series of molecular and cellular cascades whose nature and connections remain unknown. Therefore, it is unlikely that treatments directed at amyloid-b will have major clinical effects in the later stages of the disease. We discuss the two major candidate therapeutic targets to lower amyloid-b in a preventive mode, i.e., gamma- and beta-secretase; the rationale behind these two targets; and the current state of the field.