Newly identified gene mutation raises Alzheimer risk

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Mutations in a region of the gene that codes for VEGF, a protein that stimulates blood vessel growth, are associated with to a heightened risk of developing Alzheimer’s disease, Italian researchers report. They suggest that these mutations may interfere with the normally neuroprotective effects of VEGF.

The researchers analyzed the promotor region of VEGF, or vascular endothelial growth factor, in 249 patients with Alzheimer’s disease and 347 healthy subjects who served as a comparison groups. The findings are published in the Annals of Neurology.

Dr. Roberto Del Bo, from the University of Milan, and colleagues found that the distribution of two gene mutations differed between the patients with Alzheimer’s disease and the healthy controls.

Further analysis showed that one of these mutations, -2578A/A, appeared to raise the risk of Alzheimer’s disease and that this was unrelated to the presence of the apolipoprotein E genotype, the major known genetic risk factor for Alzheimer’s disease.

In further analysis of 96 Alzheimer’s disease patients and 49 healthy controls, the investigators found that the blood levels of VEGF did not differ significantly between the groups.

These findings suggest that genetic mutations “within the promoter region of the VEGF gene confer greater risk for Alzheimer’s disease, probably by reducing its neuroprotective effect,” the investigators state. The results also “confirm the biological role of VEGF in neurodegenerative processes.”

SOURCE: Annals of Neurology, March 2005.

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