APOE and Alzheimer disease: Although genetic polymorphisms in APOE and a growing number of other genes are important risk factors of late onset AD, at least two features of late onset AD that cannot be explained by linkage analysis are (i) divergences between amyloid beta and tau pathological deposits and severity of clinical disease-specific manifestations [10,13,87], and (ii) the general variability of progression rates and phenotypes [6,88,89].