SF scientists erase Alzheimer-causing gene in human brain

In this May 19, 2015, file photo, R. Scott Turner, Professor of Neurology and Director of the Memory Disorder Center at Georgetown University Hospital, points to PET scan results that are part of a study on Alzheimer's disease at Georgetown University Hospital in Washington. less In this May 19, 2015, file photo, R. Scott Turner, Professor of Neurology and Director of the Memory Disorder Center at Georgetown University Hospital, points to PET scan results that are part of a study on ... more Photo: Evan Vucci / Associated Press 2015 Photo: Evan Vucci / Associated Press 2015 Image 1 of / 27 Caption Close SF scientists erase Alzheimer-causing gene in human brain 1 / 27 Back to Gallery

Scientists in San Francisco may be close to finding a cure for Alzheimer's disease. The key to their success was looking not at the brains of mice – a standard practice in scientific research – but of men.

Researchers at Gladstone Institutes, an independent biomedical research institution in San Francisco, have discovered the cause of the primary genetic risk factor for Alzheimer's disease, and they may have found a solution to erase its damaging effects.

Their findings, published Tuesday in the journal Nature Medicine, are especially important because they conducted tests not on the brains of mice, but that of humans.

The scientists found human brains that possess even one copy of a gene, called apoE4, are more than twice as likely to develop Alzheimer's disease in their lifetimes. Having two copies increases the risk twelvefold.

ApoE4 in the human brain increases production of the amyloid beta protein, the researchers discovered. This revelation was especially surprising because past studies found that the apoE4 gene in mouse brains did not lead to an increase in amyloid beta. Excessive amyloid beta in the brain can clump together and create plaques, which can disrupt neuron firing and lead to symptoms associated with Alzheimer's.

"One concern within the field has been how poorly these mouse models really mimic human disease," said lead study author Yadong Huang, a senior investigator and director of the Center For Translational Advancement at Gladstone, in a statement. Huang noted that "many drugs work beautifully in mouse models," but come up short in tests on human brain tissues.

To correct the accumulation of harmful proteins, the scientists looked to alter the gene that produces such proteins, apoE4. By treating the human apoE4 neurons with a structure corrector – a compound that changes the shape of the apoE4 gene to resemble a similar, but innocuous gene – the scientists restored normal function to the brain cells.

The next step is working with the pharmaceutical industry to test the structure correctors on human patients.

"Drug development for Alzheimer's disease has been largely a disappointment over the past 10 years," said Huang. His team hopes to change that.

Michelle Robertson is an SFGATE staff writer. Email her at mrobertson@sfchronicle.com or find her on Twitter at @mrobertsonsf.