Alzheimer’s disease (AD) is a progressive and ir­re­v­ersible neu­rodegenerative disor­der, char­ac­terized by dis­tinct neu­ropatho­logical le­sions. These include extra­cellular deposits of β amyloid (Aβ) in se­nile plaques, accumu­lation of intra­neu­ronal neu­rofib­rillary tan­gles and profound neu­ronal death. Clin­ical symptoms include the inability to encode new mem­o­ries as well as cognitive and behav­ioral impair­ments. This incur­able, terminal disease af­fects some 35 millions of people worldwide. With a rapidly aging society in the west­ern countries this number is expected to grow so that 1 in 85 people will be af­fected by 2050.

The cause and progres­sion of Alzheimer's disease are not well under­stood. By an­alyzing activ­ity of cortical neu­rons in a mouse model of AD we have re­cently shown that in vivo the vicin­ity of an amyloid plaque is enriched with hy­per­active, syn­chronously spiking neu­rons (see First direct look into the in vivo neuronal activity in the vicinity of Alzheimer-plaques, Busche et al., Sci­ence 2008). The aim of the present project is to study mech­a­nisms under­lying this hy­per­activ­ity, the impact of hy­per­active neu­rons on cognitive behav­ior of mice and to re­veal/test pharma­co­logical substances capa­ble of reduc­ing neu­ronal hy­per­activ­ity.