Plasma biomarkers, such as Aβ40, Aβ42 and phosphorylated tau, offer a promising tool for diagnosing Alzheimer's disease (AD), recruitment for clinical trials and monitoring the disease progression and treatment outcome in people living with the disease. However, whether these plasma biomarker levels change with the time of the day is still unknown. In a new study published in the journal of Translational Psychiatry (Nature), a team of researchers led by Dr Derk-Jan Dijk from the Surrey Sleep Research Centre, University of Surrey (UK), investigated whether timing could affect plasma biomarker levels and, therefore, AD diagnosis and monitoring of disease progression.
This research involved 38 participants of which eight were people living with mild AD, six were partners, carers or supporters of people with AD and 24 were cognitively healthy adults. All the participants were aged between 50 and 85 years old. Cognitively healthy participants were recruited via the Surrey Clinical Research Facility Database. Participants with mild AD were approached via Surrey and Borders Partnership NHS Foundation Trust memory services. After a screening visit to assess eligibility, participants attended a clinical facility and took part in two studies. In the first study, participants had two blood samples drawn, one sample collected in the evening and another in the morning. In the second study, blood samples were drawn at three-hour intervals starting nine hours before habitual bedtime and continuing 15 hours after habitual bedtime.
Researchers found that, in the second study, there was a significant effect of the time of the day when blood samples were collected for all biomarkers analysed. In general, the lowest values were observed in the morning. In the case of p-tau217, the lowest values were observed in the morning after wake-up time, whereas the highest levels were reported in the afternoon and evening. For Aβ40, Aβ42 and NFL, peak levels were observed during the nocturnal sleep period whereas lowest levels occurred in the morning hours (upon waking for Aβ40 and Aβ42, and in mid-morning for NFL). A significant effect of the group of participants was observed for p-tau217 with the highest levels observed in participants with mild AD. Although this study shows that levels of commonly used plasma biomarkers in dementia research vary with the time of the day when samples are collected and despite the presence of factors such as light/dark cycle, sleep/wake state and meals, larger sample sizes are needed to determine the shape of this variation, the difference across biomarkers and the factors responsible for this variation. Until then, researchers recommend that the reference limits for biomarkers used in dementia research are established in samples collected while fasting and in the morning.