Looking Behind the Curtain: Patient Stratification According to Genetic or Demographic Factors May Yield Unexpected Results in Studies of Neurodegenerative Diseases

Abstract

Amyloid-PET studies of neurodegenerative diseases may yield inconclusive findings due to lacking stratification according to genetic or demographic variants. APOE ɛ4 alleles are the major variants to increase disease susceptibility and cause earlier onset and more behavioral features in patients with late-onset Alzheimer’s disease, but have no linear effects on cognitive or functional decline; thus, sample stratification according to APOE ɛ4 carrier status may be the best option. Interactions among APOE ɛ4 alleles, sex, and age on amyloid-β deposition may reveal even more innovative findings with sufficiently large samples, suggesting variable genomic effects of cognitive reserve, sex differences, and cerebrovascular risk on neurodegeneration.