Rapamycin as a Novel Therapeutic for Alzheimer's Disease: Prevention Assessed Through Neuroimaging

Alzheimer's disease (AD) is the sixth leading cause of death in the United States. Although AD research is bustling, a concrete and effective treatment has yet to be discovered. This study aimed to assess vascular magnetic resonance imaging (MRI) as an early detection method for AD, and to then test the potential of FDA‐approved drug Rapamycin (Rapa) in treating pre‐symptomatic AD. Rapa is capable of increasing lifespan in mammals and inhibiting unwanted cell mobility, such as cancer cell growth. This study is the first to connect Rapa's capabilities with AD. In order to analyze Rapa's efficacy, neuroimaging and behavioral tests were conducted on mice that carry the apolipoprotein E4 gene (APOE4), the strongest genetic risk factor for AD. Methodology included MRI, magnetic resonance spectroscopy (MRS), Blood‐Brain Barrier (BBB) integrity and neuroinflammation determinations, Radial Arm Water Maze (RAWM), and Novel Object Recognition Test (NOR). These methods provided a comprehensive analysis of the subjects' neurological health and cognitive functions by giving insight into cerebral blood flow, brain metabolites, spatial memory, recognition memory, and neuroinflammation. Vascular MRI effectively pinpointed vascular defects and therefore accurately identified early AD. Data strongly supported the initial hypothesis that with the introduction of Rapa, APOE4 mice will show improved cognition, memory, and neurological health. Cerebral blood flow and crucial brain metabolites were restored in Rapa mice; Rapa mice exhibited cogent memory in comparison to their counterparts in cognitive tests; Rapa reduced neuroinflammation‐‐all with significance. Thus, vascular neuroimaging is a promising early AD detection technique and Rapa holds high potential in preventing AD development. Support or Funding Information The work was supported by funding from the National Institute on Aging (NIA) of NIH (K01AG040164 to A‐LL) and NIH CTSA at the University of Kentucky (UL1TR0000117; pilot grant to A‐LL).