A brain multi-omic approach to identify key molecular drivers of neuropsychiatric

点击翻译按钮获取中文摘要

Approximately 65% of individuals with mild cognitive impairment (MCI), Alzheimer's disease (AD), or AD related dementias (ADRD) experience neuropsychiatric symptoms (NPS). These debilitating symptoms include depression, anxiety, apathy, delusions, hallucinations, agitation, sleep disturbances and are associated with faster disease progression, greater functional impairment, higher caregiver burden, and earlier institutionalization. Current treatments for NPS in MCI/dementia have limited efficacy but high rates of adverse side effects, including higher mortality. Therefore, safe and effective treatments for NPS are urgently needed. However, we have limited insights into molecular mechanisms of NPS in MCI/dementia to nominate therapeutic targets. To address this knowledge gap, we aim to elucidate the genetic and molecular mechanisms underlying NPS in MCI/dementia using two complementary but independent approaches. Our proposed plan was to use tandem mass tagged-based proteomics; however, since the submission of the proposal and the awarding of funding, the equipment at the Emory Core Proteomics facility is now committed to many new NIH-funded projects. The consequence of these newly awarded projects is reduced capacity of the Core to complete our proposed aims at the proposed timeline. This supplement will support the timely throughput of the whole brain proteomics by proposing to lease-to-own a liquid chromatography coupled to a mass spectrometer to complete the proposed specific aims following the proposed timeline.