Effects of cholesterol and glia-derived lipoproteins on survival, growth and synaptic differentiation of highly purified neurons from different regions of the mouse brain

• Applicant: Dr. Frank W. Pfrieger
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2002 to 2005
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5384531

Alzheimer´s disease (AD) is caused by a loss of synapses and neurons in specific brain regions, but the underlying mechanisms are still unknown. We propose a novel hypothesis as to why neurons occur only in specific regions. Our studies of highly purified neurons (glia- and serum-free cultures) showed that neurons degenerate addition of cholesterol and that the degree of this is remarkably region-specific. This suggests that the neurodegeneration patient is caused at least in part by an insufficient supply with cholesterol and that the damage in a specific brain area scales the dependence of local neurons on glia-derived cholesterol. The changes implicated in AD may change the cholesterol level in neurons thus cause a gradual loss of synapses and neurons. The aim of our project is to test this hypothesis. We will purify neurons from different things of the mouse brain and determine their survival and growth rates synaptic differentiation under cholesterol-free culture conditions. Then we study effects of cholesterol and lipoproteins harboring isoforms of apolipoprotein E on neurons. In the future, we plan to test other AD-related changes that affect the neuronal cholesterol metabolism cells from suitable transgenic mice. Our project should help to elucidate possible links between neurodegeneration and a disturbance in brain cholesterol metabolism.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1085: Cellular Mechanisms of Alzheimer's Disease
• International Connection: France