We have developed the first functional zebrafish model of memory loss in Alzheimer's disease, AD. These "demented" fish have lost their ability to learn simple escape behavior after injection of amyloid β, Aβ, into the brain. In Aβ-treated animals, increased neuronal death is also seen and inhibition of caspases and p53 shows that the learning problems are caused by cell death. We have also observed colocalization of fluorescent Aβ in dead neurons and microglia in vivo. We have further injected fish with brain extracts from Alzheimer patients and patients without dementia. Animals injected with AD brain cannot learn, while those injected with healthy brain have normal learning. This is the first time it has been shown that memory problems can be induced by brain extracts from AD patients. We are now further investigating how Aβ leads to neurodegeneration. We follow the formation of plaques, how neurons are killed and how microglia interact with the plaques. Important genes for the disease process are knocked out and learning ability/cell survival is measured. An interesting finding is that the learning ability in Aβ-injected animals returns after a few days, as previously observed in rodents. We believe that the mechanisms, such as clearance or regeneration, could be the basis for future patient treatment. We will also use the new model to screen future drugs and rapidly test genetic and clinical findings from patient material.