Increased Expression of Kif11/Kinesin‐5 mRNA Offsets Cognitive Deficits In An Alzheimer’s Mouse Model, Blocks Aβ‐Mediated Decreases in Long‐Term Potentiation and Spine Density, and is Associated With Better Cognitive Performance in Alzheimer’s Patients

Background Interactions between the Aβ with intra- and extra-cellular molecules disrupt neuronal structures functions, leading to cognitive dysfunction in Alzheimer’s disease (AD). We previously have shown that competitively inhibits microtubule motor protein KIF11 (Kinesin-5/Eg5), which regulates dynamics, cellular trafficking, migration, important for learning memory. In vitro cell culture ex vivo electrophysiology experiments later revealed inhibition of by underlies multiple phenotypes associated AD, including decreases LTP, breakdown network, deficits neurotransmitter receptor localization function. Here we aimed determine whether increased Kif11 expression overrides AD. Methods overexpressing mice were crossed 5xFAD mouse model AD generate overexposes Kif11. Learning memory these was measured through performance 6-8 month old radial-arm water maze LTP fEPSP response high-frequency stimulation CA1 region hippocampal slices our transgenic mice. Primary rat neurons transiently transfected express human APP harboring Swedish mutation (APPswe) or without overexpression affects Aβ-mediated dendritic spine, then evaluated function amyloid positive individuals ROS/MAP study their mRNA 4 brain regions, DLPFC (N = 939), PCC 527), CN 715). Results toxicity rescues spine density cultured neurons. Furthermore, found spatial working prevented a overexpresses Analyses RNAseq data from participants Religious Order Study Memory Aging (ROS/MAP) higher patients correlated better performance. Conclusion is essential maintaining synaptic functions critical preventing overriding inhibitory interaction could be promising therapeutic target phenotypes.