Gene targeting prevents memory loss in Alzheimer’s disease model

Northwestern University researchers have prevented learning and memory deficits in a model of Alzheimer’s disease using a gene-targeting approach to block production of beta-amyloid, or “senile,” plaques, one of the hallmarks of the disease.

Alzheimer’s disease is a neurodegenerative condition affecting over 15 million people worldwide that causes memory loss and, ultimately, dementia. Some research suggests that Alzheimer’s disease is caused by an increased amyloid burden in the brain — the so-called amyloid cascade hypothesis.

Results of the Northwestern study, published in the January issue of the journal Neuron, provide compelling evidence for the therapeutic potential of inhibiting an enzyme, beta-secretase (BACE1), required for the production of beta-amyloid, to treat memory impairment in patients with Alzheimer’s disease.

The study also presents new evidence that beta-amyloid is directly responsible for causing the memory-robbing effects of Alzheimer’s disease, said Masuo Ohno, research assistant professor of physiology, Feinberg School of Medicine at Northwestern University. Ohno’s co-researchers on the project were John F. Disterhoft, professor of physiology, and Robert Vassar, associate professor of cell and molecular biology at the Feinberg School.

Ohno and colleagues used behavioral, biochemical and electrophysiologic methods to analyze BACE1 in mice bred to lack the enzyme but to also overproduce amyloid precursor protein, which BACE1 “clips” into fragments of beta-amyloid that eventually form the notorious plaques associated with Alzheimer’s disease.

The mice were healthy and had no serious neurological abnormalities, suggesting that BACE1 inhibition is a rational strategy for treating Alzheimer’s disease, Ohno said.

Importantly, the beneficial effects of BACE1 inhibition in the mice were seen well before beta-amyloid plaques formed, indicating that the soluble forms of the protein can disrupt learning and memory in early stages of the disease process.

“Potential compounds that block BACE1 should be useful in counteracting the Alzheimer’s disease process. We clearly show for the first time that genetic reduction of brain beta-amyloid levels prevents memory deficits and brain cell functional abnormalities in a laboratory model of Alzheimer’s disease,” Ohno said.

“This well-executed study in mice is another step forward toward demonstrating the validity of anti-amyloid interventions in Alzheimer’s disease. The next step is to see if this works in more sophisticated models of the disease, and eventually in humans. ” said William Thies, vice president of medical and scientific affairs for the Alzheimer’s Association, which funded part of the study. The National Institutes of Health also funded the study.

Media Contact

Elizabeth Crown EurekAlert!

Further information:

http://www.nwu.edu

All news from this category: Life Sciences

Articles and reports from the Life Sciences area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Back to the Homepage

Comments (0)

Write comment

Latest posts

Bringing atoms to a standstill: NIST miniaturizes laser cooling

It’s cool to be small. Scientists at the National Institute of Standards and Technology (NIST) have miniaturized the optical components required to cool atoms down to a few thousandths of…

Record-breaking laser link could help us test whether Einstein was right

Scientists from the International Centre for Radio Astronomy Research (ICRAR) and The University of Western Australia (UWA) have set a world record for the most stable transmission of a laser signal through…

Adaptive optics with cascading corrective elements

A cascaded dual deformable phase plate wavefront modulator enables direct AO integration with existing microscopes–doubling the aberration correction range and greatly improving image quality. Microscopy is the workhorse of contemporary…

Partners & Sponsors

By continuing to use the site, you agree to the use of cookies. more information

The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.

Close