1 What form of Abeta cause AD? What is the mechanism?Target: ADDL Synuclein? LTP or LTD ADDL reduce LTP Synuclein reduces LTP? Disease relevance Mouse models K-channels A-current Proteins Genes Dataset/ Source: SWAN ModelDB BrainPharm GenSat Questions: What form of Abeta cause AD? How does ADDL impair synaptic plasticity? What cell types are affected? Go to next slide Does LTP occur in the right place? Right cell type? Channel  cell type What is the mechanism? Go to slide 3 What genes and proteins are involved? Gene expression patterns AllenBrain PubMed Alzgene Which genes are expressed in the relevant part of the brain?

2 2: driving question Brain Pharm ADCA1 NeuronDBHow does ADDL impair synaptic plasticity? What cell types are affected? Brings to mechanism question Brain Pharm ADCA1 NeuronDB CA1extracellularAbeta CA1has currentA-current A-currenthas channelK+ Missing datasets Currents that have K+ ions are conducting K+ channels? CA1LTP

3 3: mechanisms K-channels  proteins K-channels genes CA1LTPLTPpapers MeSH “LTP” and “K-channel” co-localization network PubMed : Kv4.2 pmid: PaperGene Orthomap AlzGene: Potassium channel gene  HilleWashUchannel database EntrezgenePubMed GeneRIFSPubMed Jax synaptic plasticity Jax hippocampal biology