Alzheimer‘s disease (AD) is the most common dementia associated with brain inflammation. Aducanumab is the first disease-modifying therapeutics approved by the US-FDA for mild AD patients. Improvements of neuronal plasticity and neural networks in dementia are the next stage of mild AD drug development. However, none of the improvers in neurotransmission failed to prevent the progression to AD. We here introduced the novel improver of brain function through T-type calcium channel activation. Reduced T-type calcium channel levels are reported in aged brain and its inhibition by Abeta oligomers impair spine formation in the brain. We developed T-type calcium channel enhancer SAK3 which activates calcium currents in Neuro2A cells overexpressed Cav3.1 and Cav3.3 but not Cav3.2 channels. SAK3 promoted the hippocampal long-term potentiation (LTP) through CaMKII activation. CaMKII activation in the hippocampus and cortex were also associated with improvement of spine morphology in APP knock-in mice. The proteasome activation possibly mediated CaMKII dependent phosphorylation of Rpt-6 subunit of 19S proteasome in APP knock-in mouse brain. Enhancement of T-type calcium channel in neuroprogenitor cells in the hippocampus was accounted for improvement of neurogenesis, thereby ameliorating depressive behaviors. the diagnostic technology defined early mild dementia patients is critical for promoting clinical development of disease-modifying therapeutics. In the symposium, we also discuss the novel diagnostic technology for mild AD to define brain inflammation.