Use of AD Informer Set compounds to explore validity of novel targets in Alzheimer's disease pathology.
Frances M PotjewydJoel K Annor-GyamfiJeffrey AubéShaoyou ChuIvie L ConlonKevin J FrankowskiShiva K R GuduruBrian P HardyMegan D HopkinsChizuru KinoshitaDmitri B KireevEmily R MasonCharles T MoerkFelix NwogboKenneth H PearceTimothy I RichardsonDavid A RogersDisha M SoniMichael StashkoXiaodong WangCarrow WellsTimothy M WillsonStephen V FryeJessica E YoungAlison D AxtmanPublished in: Alzheimer's & dementia (New York, N. Y.) (2022)
We have demonstrated the utility of the AD Informer Set in the validation of novel AD hypotheses using biochemical, cellular (primary and immortalized), and in vivo studies. The selectivity for their primary targets versus essential GPCRs in the brain was established for our compounds. Statistical changes in tau, p-tau, Aβ40, and/or Aβ42 and blood-brain barrier penetrance were observed, solidifying the utility of specific compounds for AD. Single-concentration phagocytosis results were validated as predictive of dose-response findings. These studies established workflows, validated assays, and illuminated next steps for protein targets and compounds.