Association between Lower Body Temperature and Increased Tau Pathology in Cognitively Normal Older Adults

Abstract

Background Rodent model and in vitro studies suggest body temperature (Tb), and consequently brain temperature, has the potential to bidirectionally interact with tau pathology in Alzheimer’s Disease (AD). Tau phosphorylation is substantially increased by small (< 1°C) reductions in temperature within the human physiological range, and lower brain thermoregulatory areas may be among those first affected by AD pathology. Here, we evaluated whether Tb (as a proxy for brain temperature) is cross-sectionally associated with clinically utilized markers of tau pathology in cognitively normal older adults. Methods Tb was measured with ingestible telemetry continuously over 48 hours, including two nights of nocturnal polysomnography to delineate whether tau pathology is differentially associated with Tb during waking vs sleep. Tau pathology was assessed with plasma and cerebrospinal fluid (CSF) tau phosphorylated at threonine 181 (P-tau), sampled the day following Tb measurement, as well as neurofibrillary tangle (NFT) burden in early Braak stage areas, imaged with MR-PET using the [18F]MK-6240 radiotracer on average one month later. Results Plasma and CSF P-tau levels were highly correlated with one another, and with tau tangle radiotracer uptake. Lower Tb, as quantified by lower mean Tb and a greater proportion of time Tb was under 37.0°C, was associated with increased NFT burden and increased plasma and CSF P-tau levels. NFT burden was associated with lower Tb during waking, but not during sleeping intervals. Conclusions Preliminary results suggest that lower Tb in older adults may be associated with increased soluble and aggregated tau pathology.