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Source: Corinna Kaarlela
415-476-2557
11 September 1998
MOUSE STUDY REVEALS EFFECTS OF APOE4 PROTEIN ON ALZHEIMER’S DISEASE
Researchers at the Gladstone Institute of Neurological Disease and UC San Francisco have conducted a study in mice that offers insight into why people who inherit two copies of the apolipoprotein E4(apoE4) gene have a much greater risk of developing Alzheimer's disease than people with two copies of the most common variation of the gene, apoE3. The genetically engineered mice could be ideal, they said, for testing drugs aimed at preventing the detrimental effects of apoE4.
In their study, the researchers generated strains of mice that expressed either human apoE4 protein or human apoE3 protein in their brains. The mice were either allowed to age normally or were treated with excitatory amino acids, which are presumed to contribute to a number of neurodegenerative conditions.
The researchers then analyzed the density and integrity of the nerve cell processes in their brains by staining sections with fluorescently labeled antibodies and analyzing the sections with high-resolution microscopy.
Significantly, apoE3 mice maintained normal nerve cell processes (bottom left panel). In contrast, the nerve cells in apoE4 mice withered away (bottom right panel). The investigators speculate that the failure of apoE4 to prevent neurodegeneration in aging mice could explain the increased Alzheimer's disease risk observed in humans carrying the apoE4 gene. Notably, the proteins differ by only one amino acid, apoE3 containing a Cys (cystein) amino acid, and apoE4 containing an Arg (argenine) amino acid.
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