Effect of age, sex, cognitive status and Apolipoprotein E genotype on plasma biomarkers of amyloid pathology

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Abstract Background Plasma biomarkers of amyloid pathology may streamline the diagnostic pathway for patients with subjective cognitive decline, MCI, AD . The influence of age, sex, cognitive status, body mass index (BMI) and apolipoprotein E (APOE ε) genotype on phosphorylated‐tau‐181 (phospho‐tau‐181) and apolipoprotein E4 plasma biomarkers was explored. Method 597 plasma samples (from the Australian Imaging, Biomarkers and Lifestyle cohort) were retrospectively analysed using the fully automated Elecsys® prototype plasma immunoassays for phospho‐tau‐181 and apolipoprotein E4 on the cobas e 601 and e 411 analysers (Roche Diagnostics International Ltd). A composite score was derived by combining phospho‐tau‐181 and apolipoprotein E4 results. Amyloid‐positron emission tomography (PET) visual read was the reference standard for defining amyloid status. The relationship between biomarker levels and potential influencing factors was assessed. Result Phospho‐tau‐181 and composite score were increased in samples from amyloid‐positive versus amyloid‐negative subjects and in dependence of cognitive status. The dependence of phospho‐tau‐181 and composite score on APOE ε genotype could largely be explained by the increased prevalence of amyloid positivity in APOE ε4 carriers compared with non‐carriers. A potential confounding relationship between sex and age and phospho‐tau‐181 or composite score was detected, which could not be fully explained by the increasing incidence of amyloid positivity with age. Apolipoprotein E4 was highest in APOE ε4 homozygotes, lower in heterozygotes and undetectable in non‐carriers. Conclusion A single cut‐off value for phospho‐tau‐181 and composite score may be used in clinical routine to determine amyloid pathology in the intended use population, regardless of age, sex and APOE ε genotype. Further evaluation is required in more diverse populations (comorbidities) and using additional biomarkers (β‐amyloid).

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