Levels of key dementia biomarkers, including phosphorylated tau, may vary significantly throughout the day, with the highest levels occurring in the afternoon and early evening, according to a recent study. 

In the study, published in Translational Psychiatry, researchers examined how the time of day affects plasma biomarkers related to dementia, specifically phosphorylated tau (p-tau217), a key biomarker for Alzheimer's disease (AD). The study involved 38 participants with an average age of 70.8 years (± 7.6 years). Participants were grouped into those with mild Alzheimer's disease (PLWA, n = 8), their partners/caregivers (n = 6), and older adults without cognitive impairment (n = 24).

The blood sampling protocols were used: one with samples collected 12 hours apart and another with samples taken every 3 hours over a 24-hour period. Using single-molecule array technology, the researchers measured levels of p-tau217, along with additional biomarkers such as amyloid-beta 40 (Aβ40), amyloid-beta 42 (Aβ42), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). 

The results demonstrated that levels of p-tau217, Aβ40, Aβ42, and NfL showed diurnal variation, with p-tau217 being lowest in the morning and peaking in the afternoon and early evening. The variation in p-tau217 levels (15.8%) was notably similar to the annual increase (14.7%) seen in participants with mild cognitive impairment who are amyloid-β positive.

Intraclass correlations for the measured biomarkers ranged between 0.76 and 0.97, suggesting that variability was greater between participants than within individual participants. For specific biomarkers: 

• p-tau217: lowest in the morning and peaked in the afternoon/evening, with a diurnal variation of roughly 15.8%
• Aβ40: had a diurnal variation around 14.0%
• Aβ42: showed a variation of approximately 15.3%
• NfL: had a diurnal change of about 10.6%
• GFAP: variation approached significance, with a change of 17.0%.

The study found that time of day significantly influenced all biomarkers except GFAP. Additionally, p-tau217 levels varied significantly based on participant group (P = .003), with the highest levels found in participants with mild AD (PLWA).

The researchers suggested that timing of blood sample collection should be standardized or considered when interpreting plasma biomarkers for dementia diagnosis and monitoring, as these levels vary throughout the day. The underlying reasons for these variations remained unclear but may be linked to factors like sleep patterns, circadian rhythms, physical activity, posture, or meals.

Full disclosures can be found in the published study.