Basic Science and Pathogenesis

We have found multiple novel roles for voltage-gated potassium channel auxiliary subunit DPP6 (Dipeptidyl Peptidase-Like 6) including in neuronal development, learning and memory and connections to Alzheimer disease (AD)/dementia. Novel structures associated with amyloid-β (Aβ) were found in hippocampal area CA1 in aging DPP6-KO mice, apparently derived from degenerating presynaptic terminals, that are significantly more prevalent in DPP6-KO mice compared to WT mice. Aging DPP6-KO mice also show increased Aβ, tau pathologies, neuroinflammation and sleep disturbances.

in vivo surgical implantation of the HD-X02 telemetry system (DSI) RESULT: The results showed twelve-month-old DPP6-KO mice have sleep disorders that include more wake and REM and less NREM duration in the light-on phase. For seizure study, aging DPP6-KO mice showed significantly increased and longer spike train durations, also exhibited a significantly higher prevalence of spike wave discharges and nonconvulsive seizures with no accompanying tonic-clonic movements compared to WT controls. We also found increase in the number of epileptiform spike events (over 400 mV) in 12-month-old DPP6-KO mice, and the epileptiform spike events were suppressed after acute administration of anti-seizure medicine levetiracetam (LEV) CONCLUSION: Together these results indicate that DPP6-KO mice have sleep disorders and seizure with epileptiform events, further supporting a role of DPP6 in Alzheimer's/dementia.