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.