CSF biomarkers in Alzheimer's disease and controls: associations with APOE genotype are modified by age.

The object of this study was to elucidate the effect of age in the relationship between APOE genotype and CSF biomarkers amyloid-beta1-42 (Abeta42), total tau (tau) and tau phosphorylated at threonine 181 (ptau-181) in AD and controls. 302 AD patients and 174 controls were categorized into APOE epsilon4 carriers and non-carriers, and into younger and older (65years). In controls, older age and APOE epsilon4 were independently associated with lower Abeta42 and higher tau and ptau-181 levels (p < 0.05). For tau and ptau-181, there were also interactions (p < 0.10): older carriers had higher levels than older non-carriers, without effect for younger controls. In AD, APOE epsilon4 genotype had a main effect on Abeta42, but there was also an interaction: older carriers had lower Abeta42 than older non-carriers, without effect for younger AD patients (p < 0.05). For tau and ptau-181, there were only interactions: older carriers had higher levels than older non-carriers, while younger AD patients showed the opposite (p 0.05). Association between CSF biomarkers and APOE genotype were modified by age in both controls and AD patients. This suggests that cognitively healthy APOE epsilon4 carriers are more prone to develop AD pathology with aging. For AD patients, this provides support for the existence of subtypes within the disease.