A recent study on the effect size of the major susceptibility gene for AD, APOE ε4, supports this reasoning; when disregarding clinical information on patients with cognitive impairment and simply grouping them on the basis of CSF tau and Aβ markers, the association of APOE ε4 with AD was twice as strong as compared to when classifying patients according to clinical status [74]. This evidence concerns the gene MAPT and Alzheimer disease.