Affiliations: [a] Alzheimer Center and Department of Neurology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands | [b] Department of Clinical Chemistry, VU University Medical Center Amsterdam, Amsterdam, The Netherlands | [c] Department of Epidemiology and Biostatistics, VU University Medical Center Amsterdam, Amsterdam, The Netherlands
Correspondence:
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Corresponding author: Maartje I. Kester, Alzheimer Center, Department of Neurology, VU University Medical Center Amsterdam, PO box 7057, 1007 MB Amsterdam, The Netherlands. Tel.: +31 20 44400685; Fax: +31 20 4440715; E-mail: m.kester@vumc.nl.
Note: [] Communicated by Sanna-Kaisa Herukka
Abstract: The object of this study was to elucidate the effect of age in the relationship between APOE genotype and CSF biomarkers amyloid-β1–42 (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.
