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-β_1–42 (Aβ₄₂), 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 ε4 carriers and non-carriers, and into younger and older (⩾65years). In controls, older age and APOE ε4 were independently associated with lower Aβ₄₂ 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 ε4 genotype had a main effect on Aβ₄₂, but there was also an interaction: older carriers had lower Aβ₄₂ 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 ε4 carriers are more prone to develop AD pathology with aging. For AD patients, this provides support for the existence of subtypes within the disease.