Hyperexcitable Circuits in the Etiology of Psychosis in Alzheimer's Disease

Our study suggests that this selective vulnerability of supragranular excitatory neurons may in part be driven by glial inflammatory programs triggered by differential layer-specific neuropathological changes observed in AD+P. Unexpectedly, we found that these compensatory mechanisms may in fact further exacerbate pathology and network dysfunction. Our study provides novel insight into the pathophysiological role of hyperexcitable circuits in the etiology of neuropsychiatric symptoms of AD, and identifies new genetic targets in the search for new classes of antipsychotic treatments.