The gene plays a major role in the growth and remodelling of vascular systems, say researchers at the University of Rochester Medical Center. But, in brain cells of people with Alzheimer's disease, expression of the gene is low, the scientists found, revealing a new piece of the Alzheimer's puzzle.
In laboratory studies, the scientists also showed that restoration of the gene expression level in the human brain cells stimulated the formation of new blood vessels. It also increased the level of a protein that removes amyloid beta peptide, the toxin that builds up in brain tissue in Alzheimer's disease.
The scientists at the Department of Neurosurgery, led by Berislav Zlokovic, M.D., Ph.D., deleted one copy of the gene in mice, creating echoes of the damage of Alzheimer's, including reduced ability to grow blood vessels in the brain and impaired clearance of amyloid beta.
The gene targeted in the research is a homeobox gene known as MEOX2 and also as GAX. A homeobox gene encodes proteins that determine development. Zlokovic calls it a "big boss."
The scientists studied human brain endothelial cells taken from autopsy samples from people with Alzheimer's. They found that expression of MEOX2, or mesenchyme homeobox 2, is low in the cells of those with Alzheimer's. "The cells with low levels can't form any kind of vascular system or any kind of network," Zlokovic said. "They just start dying."
In restoring expression of the gene, the Rochester scientists showed for the first time that it suppresses a specific transcription factor. When the expression of MEOX2 is low, the factor "rampages" and allows apoptosis or programmed cell death in the brain vascular system, Zlokovic said.
When MEOX2 expression is low, the research also showed that a protein that helps with the clearance of amyloid beta is suppressed. Zlokovic views the findings as support for his belief that Alzheimer's is a neurovascular disease.
MEDICA.de; Source: University of Rochester Medical Center