Introduction: genetic determinants of mid- and late-life dementias

We introduce a series of papers dealing with genetic aspects of a subset of dementias of mid-life and late-life in order to illustrate four principles. First, there appear to be many genetic loci with the potential to modulate susceptibility to such dementias. Second, most of those so far discovered are autosomal dominants and none are autosomal recessives. Third, the autosomal dominant mutations are individually rare. Their frequencies in a given population are likely to be functions of genetic drift. Fourth, despite their rarity, they may inform us about the pathogenesis of more common late-life dementias, notably dementias of the Alzheimer type, which have polygenic determinants. The most important such modulation so far discovered involves polymorphic forms of the APOE locus.