Initially, amyloid plaque pathology in AD was thought to correlate positively with clinical progression of the disease [5] until the toxic effects of soluble beta-amyloid (Aβ) peptides, both Aβ1-40 and Aβ 1-42, were strongly associated with cognitive decline even in the absence of significant tau pathology [6]. The gene discussed is MAPT; the disease is Alzheimer disease.