While genetic studies clearly implicate amyloid as the initiating factor in AD, the correlation of tangles with neuronal loss in AD brain, together with the lack of neuronal loss and tangle formation in APP transgenic models, and the lack of efficacy with Aβ-directed therapeutics have contributed to the idea that tau pathology is an important contributor to dementia downstream of Aβ [18]. The gene discussed is APP; the disease is dementia.