Milestone Review: The History of Molecular Genetics Analysis of Alzheimer's Disease

Alzheimer research has been driven by genetic findings: from the 1990s until about 2005, by the identification of amyloid precursor protein (APP) and presenilin (PSEN) mutations, leading to the formulation of the amyloid hypothesis, and then from ~2007 by genome-wide studies which have led to the increasing appreciation of the importance of microglial insufficiency in the disease pathogenesis. These genome findings have led not only to key mechanistic insights but also to progress in the use of genetic data to predict those at high risk of the disease so that earlier treatment becomes more practical. In this review I will outline these developments and attempts to synthesise the findings into a coherent single view of the disease.