1022 Elevated Plasma Alkaline Phosphatase and Actigraphy-Derived Sleep Measures in an Aging Population

Abstract Introduction Sleep and circadian disturbances are early physiological changes observed in Alzheimer’s disease (AD) and Alzheimer’s disease–related dementias (AD/ADRD). Alkaline phosphatase (AP), an enzyme involved in vitamin D and calcium metabolism, is elevated in AD and contributes to inflammation, impaired calcium signaling, and weakened blood–brain barrier integrity. However, the relationship between circulating AP levels and objective sleep metrics remains unclear. This study examined whether AP levels are associated with sleep duration and sleep fragmentation in older adults. Methods A total of 366 Black adults (67% female; mean age = 65 years) enrolled in the NIH-funded MOSAIC sleep study provided blood samples between January 2020 and December 2025. Plasma samples from a subset of 44 participants were classified into two groups [high-AP (> 129) (n = 21) and normal-AP (40.0 - 129.0) (n = 23)], based on clinical guidelines. Wrist actigraphic data was collected for up to 7 days. Mean nightly sleep duration (minutes) and mean number of awakenings were derived using a standard scoring algorithm. Pearson correlation analyses in Microsoft Excel assessed associations between AP levels and sleep outcomes. Results Participants in the high-AP group slept an average of 298.32 minutes per night, compared with 388.13 minutes in the normal-AP group (approximately 5.0 vs. 6.5 hours). The high-AP group also exhibited a slightly higher mean number of awakenings (7.97 vs. 7.67). AP levels explained 17% of the variance in sleep duration (R² = 0.1705), with a positive correlation within the high-AP range (ρ = 0.413). In the normal-AP range, AP levels showed a weak inverse relationship with sleep duration (R² = 0.0421; ρ = −0.205). Associations between AP and sleep fragmentation were negligible across both groups, with very small R² values and weak correlations. Conclusion These preliminary findings indicate that elevated plasma AP correlated with shorter sleep duration among older adults. Larger-scale research should investigate epigenetic and biochemical pathways through which AP may influence calcium and vitamin D signaling and downstream circadian regulation relevant to AD/ADRD risk. Support (if any) NIH T32 CrossROADS Program National Institute on Aging (NIA) (T32AG081170) NIH MOSAIC R01(UE5GM155929)