The biology and pathobiology of tau protein

Abstract

The cytoskeleton-associated protein tau has a remarkably varied repertory of cellular functions in neurons in both health and disease. Although tau is classically thought of as a neuronal phosphoprotein that stabilizes axonal microtubules (MTs), it interacts with diverse signaling pathways via proteins in the cortical cytoskeleton as well and plays important roles in several aspects of axonal development and function. Abnormalities in non-MT-associated functions of tau are increasingly thought to be involved in the pathogenesis of neurodegenerative disease in humans, which is the focus of this monograph. I will first summarize normal tau interactions with other proteins and cellular functions as we currently understand them in the context of tau structure and expression patterns and discuss how these are altered in the context of neurodegenerative disease at the molecular, cellular, and organismal levels. Particular attention is given to recent studies of the cellular and intercellular aspects of tau misprocessing and their implications for the pathogenesis of human neurodegenerative disease.