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-beta(1-42) (A beta(42)), 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 epsilon 4 carriers and non-carriers, and into younger and older (>= 65years). In controls, older age and APOE epsilon 4 were independently associated with lower A beta(42) 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 epsilon 4 genotype had a main effect on A beta(42), but there was also an interaction: older carriers had lower A beta(42) 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 epsilon 4 carriers are more prone to develop AD pathology with aging. For AD patients, this provides support for the existence of subtypes within the disease.