The impact of pre-analytical factors on plasma biomarkers for Alzheimer's disease: The ASPREE Healthy Ageing Biobank

Background The conditions under which samples were collected, processed, and stored in biobanks may influence Alzheimer's disease (AD) biomarker levels. Objectives This study aims to investigate whether a range of pre-analytical factors influence plasma levels of AD biomarkers. Methods Data were obtained from the ASPREE Healthy Ageing Biobank, a cohort of healthy community-dwelling older individuals aged 70+ years in Australia. Five biomarkers were measured using plasma from 11,868 individuals: phosphorylated-tau181 (p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid-beta 42 and 40 (Aβ42/Aβ40). Linear regression examined the association between pre-analytical factors and biomarker levels. Results Participants were aged 70–96 years, and 54 % were female. The mean storage time for samples was 10.6 years (range: 7.7–13.5). Some significant associations were identified between pre-analytical factors and biomarkers, in particular for p-tau181, but the effect sizes were small. Weak negative associations were found between p-tau181 and the time from venepuncture to laboratory (transport) (β: −0.82, p = 0.03), laboratory processing to frozen storage (β:−1.56, p < 0.001), and total years of storage (β: −0.45, p = 0.007), while a positive association was found with intermediate storage at −20 °C/−30 °C compared to −80 °C (β: 2.24, p = 0.004). Longer fasting time was associated with higher levels of both NfL (β: 0.15, p < 0.001) and GFAP (β: 1.75, p < 0.001). Conclusion Following standard operating procedures, AD biomarkers can be measured in plasma from biobanks stored for up to 13 years, with minimal impact from long-term storage or other pre-analytical factors.