TOMM40 and APOE: Requirements for replication studies of association with age of disease onset and enrichment of a clinical trial.

A number of recent studies have not replicated the association of the translocase of the outer mitochondrial membrane pore subunit (TOMM40) rs10524523 polymorphism, which is in linkage disequilibrium with apolipoprotein E (APOE), with age of onset of Alzheimer's disease (AD). This perspective describes the differences between these later studies and the original experiments. We highlight the necessity for using standardized and informative assessment tools and processes when determining the age of development of AD or AD symptoms, and also stress that this clinical phenotype is best measured reliably in prospective studies during which subjects are monitored over time. This is true when assessing potential biomarkers for age of onset and when assessing the therapeutic potential of medicines that may delay the onset or progression of this disease.