ABSTRACT/PROJECT SUMMARY Psychotic symptoms that occur in advanced age in the absence of an acute medical condition or prominent mood symptoms can represent the late appearance of primary psychotic disorders such as schizophrenia or delusional disorder or can presage the appearance of a neurodegenerative condition such as Alzheimer’s disease (AD). An episode of non-affective psychosis late in life more than doubles the risk of subsequent neurodegenerative disease, with an average time from psychosis to AD diagnosis of 18 months. The biologic mechanisms responsible for the increased risk of dementia in those who experience psychosis are unclear. One hypothesis is reverse causality, in which inchoate neurodegeneration is responsible for psychotic symptoms that emerge in the absence of traditional cognitive hallmarks of dementia. The psychosis then heralds the inception of illness that will eventuate in cognitive decline. An increased burden of tau pathology has been associated with psychosis in AD. In the current pilot study will utilize PI-2620, a novel tau positron emission tomography (PET) ligand, together with single molecule array (SiMOA) peripheral fluid immunoassays to investigate whether there is evidence of elevations in tau biomarkers in a cohort of late-onset psychosis subjects without cognitive impairment. At the completion of this exploratory study, we will know whether there is evidence of tau pathology from high-sensitivity biomarkers in late-onset psychosis that would warrant a larger R01 study that would be focused on longitudinal outcomes assessing the influence of tau biomarker positivity on the risk of conversion to dementia over time.