INTERACTION OF APOLIPOPROTEIN-E EPSILON-4 WITH OTHER GENETIC AND NONGENETIC RISK-FACTORS IN LATE-ONSET ALZHEIMER-DISEASE - PROBLEMS PACING THE INVESTIGATOR

The Apolipoprotein E4 allele (Apo-epsilon 4) is the major susceptibili ty gene for late onset Alzheimer Disease (AD) but epidemiological data suggest that the effect of this allele is modified in different indiv iduals by genetic or environmental factors. Age and head injury are ma jor non-genetic factors modifying the Apo-epsilon 4 risk. There is con flicting data as to whether alleles of other chaperon proteins (such a s alpha-1-antichymotrypsin (ACT)) or Apo-epsilon 4 receptors (such as the VDRL receptor) modify the Apo-epsilon 4 risk for AD. We analyze pr oblems posed by genetic association studies including those of multipl e comparisons and selection of controls, the latter problem exacerbate d by the wide variations in Apolipoprotein E allele frequencies observ ed in different groups and localities.