Identification and Prioritization of PET Neuroimaging Targets for Microglial Phenotypes Associated with Microglial Activity in Alzheimer’s Disease

• Published in: ACS chemical neuroscience Vol. 13; no. 24; pp. 3641 - 3660
• Main Authors: Bartolo, Nicole D., Mortimer, Niall, Manter, Mariah A., Sanchez, Nicholas, Riley, Misha, O’Malley, Tiernan T., Hooker, Jacob M.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21-12-2022
• Subjects: Alzheimer Disease - diagnostic imaging; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Humans; Microglia - metabolism; Neurodegenerative Diseases - metabolism; Neuroimaging; Positron-Emission Tomography - methods; Proteomics; single-cell RNA sequencing; Alzheimer’s disease; positron emission tomography; microglia; neuroimaging
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/acschemneuro.2c00607

Activation of microglial cells accompanies the progression of many neurodegenerative disorders, including Alzheimer’s disease (AD). Development of molecular imaging tools specific to microglia can help elucidate the mechanism through which microglia contribute to the pathogenesis and progression of neurodegenerative disorders. Through analysis of published genetic, transcriptomic, and proteomic data sets, we identified 19 genes with microglia-specific expression that we then ranked based on association with the AD characteristics, change in expression, and potential druggability of the target. We believe that the process we used to identify and rank microglia-specific genes is broadly applicable to the identification and evaluation of targets in other disease areas and for applications beyond molecular imaging.