SAT-655 - Adipose Tissue-Expressed Tau in Cellular Metabolism and Metabolic Healthy Ageing

Tau aggregation is a cardinal pathological feature of Alzheimer’s disease (AD), with increasing levels of aggregated tau closely associated with cognitive impairment and neurodegeneration. To date, tau research has largely focused on its pathological roles within the central nervous system (CNS), leaving its physiological functions in peripheral tissues poorly understood. Emerging evidence indicates that tau is expressed outside the CNS, suggesting previously unrecognized roles in systemic biology.
Our work demonstrates that tau is robustly expressed in adipose tissue (AT), including both brown and white fat, where it exhibits functional relevance. RNA sequencing reveals abundant expression of tau in AT, with the high–molecular weight isoform “Big tau” representing the predominant tau transcript. Our findings further show that tau expression in AT is dynamically regulated during thermogenic remodelling in response to metabolic cues, implicating tau as a key regulator of energy expenditure. Proteomic analysis revealed that β-adrenergic–induced Big Tau engages with mitochondrial oxidative processes, thermogenic program and lipid metabolism. These findings raise novel questions regarding the role of adipose-derived tau in metabolic regulation, ageing, and its potential contribution to neurodegeneration. Using well-characterized mouse, human, and Drosophila adipose tissue samples, we define tau expression patterns, hyperphosphorylation across age, adiposity, and metabolic status. Furthermore, leveraging well-established Drosophila tauopathy models, we investigate whether AT-expressed tau influences systemic metabolism and adipose-brain communication.
Together, our research identifies adipose tissue as a previously unrecognized site of tau expression and regulation, positioning AT-expressed tau as a novel regulator of metabolic health and ageing.

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