Sleep and tauopathies: Effect of an anti-tau antibody

In neurodegenerative diseases known as the tauopathies (e.g. progressive supranuclear palsy, Alzheimer disease), there is progressive degeneration of specific brain regions that account for the symptoms and signs of each disease.  Accumulation of aggregated forms of the protein tau in structures known as neurofibrillary tangles and dystrophic neurites in these brain regions correlates well with functional decline in cognition, motor, and other functions. Cell to cell transmission of tau aggregates leading to brain dysfunction is one hypothesis which may account for spread of pathology and progressive brain dysfunction.  Our recent data, now “in press”, showing the effectiveness of certain anti-tau antibodies as a potential therapy, supports this hypothesis. One difficulty in assessing the effects of therapies for neurodegeneration in animals is the lack of a strong, quantifiable, physiologically relevant phenotype.  Here, we seek to further characterize preliminary findings that a mouse model of tauopathy (P301S Tau Tg mice) develops both decreased NREM sleep as well as a marked decline in delta power during non-REM (NREM) sleep.  In addition, we will determine whether an anti-tau antibody, HJ8.5, that we have found to strongly decrease tau pathology, will prevent this sleep phenotype when administered peripherally.