Structural characterization of tau conformational heterogeneity in Down syndrome

NARRATIVE The next barrier to extending the lifespan of individuals with Down syndrome is to combat the onset of Alzheimer’s disease (AD). We are motivated to characterize the spectrum of tau filament structures that develop in individuals with Down syndrome across the lifespan and with mixed neurological comorbidities such as AD, seizures and self-injurious, recurring head trauma. Outcomes of this work will provide a novel framework to develop structure-guided molecular diagnostics and therapeutics to more precisely define and treat the heterogeneous tau neuropathologies that arise in Down syndrome.