Neuropsychiatric symptoms (NPS) are core features of Alzheimer?s disease (AD) that contribute to early institutionalization and cause substantial caregiving and caregiver burden. Very few studies have examined AD- NPS and, so far, reliable treatments for NPS have not been found. Therefore, a better understanding of the molecular mechanisms and pathways underlying AD-NPS is a logical next step to identify reliable biomarkers that could lead to the development of effective therapeutics. Given that AD-NPS share some clinical features with serious mental illnesses (SMIs), such as schizophrenia and bipolar disorder, with this administrative supplement we seek funding to expand the efforts of the parent grant to study AD-NPS. More specifically, the parent grant is part of the psychENCODE and its goal is to perform multiscale integration of genomics and phenomics data by analyzing a large cohort of autopsy cases that covers the spectrum of SMI. Here, we would like to expand these efforts by adding AD and NPS-related phenotypes to our current analysis and by performing single cell profiling in additional cases to further enhance statistical power to detect molecular underpinning of AD-NPS.
In the United States, over a million people have schizophrenia with considerable morbidity, mortality, and personal and societal cost. We propose to use advanced and novel technologies to generate a broad range of genomic, epi-(Greek for `over', `above') genetic, and proteomic data collected from hundreds of postmortem brain samples from controls and from subjects who were diagnosed with schizophrenia. A particular strength of this proposal is that we will do much of this work in specific cell types that are often implicated in the disease. These data will provide a much needed resource to explore the genetic risk architecture and neurobiology of the disorder.
