Vascular gene fault may be linked to Alzheimer's disease

A fault in a gene that plays a major role in the growth of the body's vascular system may be involved in Alzheimer's disease. This error causes cells to be unable to form a blood supply system and die, supporting a belief that Alzheimer's is a neurovascular disease.

Researchers at the University of Rochester, New York, studied endothelial cells of brain blood vessels sampled from 36 autopsies, 11 of which came from deceased who had been diagnosed with Alzheimer's disease. They found that expression of a gene called MEOX2, also known as GAX, was 'barely detectable' in the cells of those who had Alzheimer's. When the gene expression in human cells was restored, new blood vessels grew and levels of a protein that clears amyloid beta peptide, a toxin which clumps causing brain lesions in Alzheimer's patients, increased.

The team's leader, Dr Berislav Zlokovic, from the University of Rochester Medical Center's Department of Neurosurgery and director of the Frank P Smith Laboratories for Neuroscience and Neurosurgical Research, stated 'the cells with low levels can't form any kind of vascular system or any kind of network. They just start dying'.

In further studies, the team removed one copy of the MEOX2 gene in mice. The result was damage similar to that seen in Alzheimer's patients. The mice had reduced blood flow and trouble removing amyloid beta peptide from their brains. In addition, the lowered gene activity led to 'dramatic reductions in blood flow that affect learning and memory', Dr Zlokovic stated. When the gene activity was restored, the mice regained the ability to construct a vascular system.

These findings could be useful for treating Alzheimer's disease. 'This is a new pathway for the study and treatment of Alzheimer's disease,' said Dr Zlokovic. 'This gene could be a therapeutic target. If we can stop this cycle, we could slow or stop the progression of the neuronal component of this disease', he added.

But, the work is far from complete. It needs to be replicated to ensure these are not chance findings. It is also unclear whether the low expression of the gene results in the death of the brain cells, or the disease in neurons results in the low expression.

The report will appear in September's print version of Nature Medicine.