Brain enzyme is double whammy for Alzheimer's disease

August 20, 2012, Sanford-Burnham Medical Research Institute
This shows beta-amyloid plaques (red) in the brain of an Alzheimer's disease patient. Credit: Sanford-Burnham Medical Research Institute

The underlying causes of Alzheimer's disease are not fully understood, but a good deal of evidence points to the accumulation of β-amyloid, a protein that's toxic to nerve cells. β-amyloid is formed by the activity of several enzymes, including one called BACE1. Most Alzheimer's disease patients have elevated levels of BACE1, which in turn leads to more brain-damaging β-amyloid protein.

In a paper published August 15 in The Journal of Neuroscience, researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) found that BACE1 does more than just help produce β-amyloid—it also regulates another cellular process that contributes to memory loss. This means that just inhibiting BACE1's enzymatic activity as a means to prevent or treat Alzheimer's disease isn't enough—researchers will have to prevent cells from making it at all.

"Memory loss is a big problem—not just in Alzheimer's disease, but also in the normal aging population," said Huaxi Xu, Ph.D., professor in Sanford-Burnham's Del E. Webb Neuroscience, Aging, and Stem Cell Research Center and senior author of the study. "In this study, we wanted to better understand how BACE1 plays a role in memory loss, apart from β-amyloid production."

To do this, Xu and his team used a mouse model that produces human BACE1. Mice produce a different type of β-amyloid, one that's far less toxic than the human version. So, in this system, they could look solely at how BACE1 functions independent from β-amyloid formation. If BACE1 only acted to produce β-amyloid, the researchers would expect to see no effect when mice produce human BACE1—since mouse β-amyloid isn't very toxic, extra BACE1 would be no big deal. Instead, they saw that the enzyme still impaired learning and memory, indicating a secondary function at work.

If it's not producing β-amyloid, what is BACE1 doing? Many years ago, scientists found that a protein in the brain—protein kinase A (PKA), better known for directing cellular metabolism—also plays an important role in memory formation. In this study, Xu and colleagues found that BACE1 disrupts the cell's production of other molecules required for PKA function. By that mechanism, BACE1 inactivates PKA and therefore inhibits memory formation in mice, even in the absence of neurotoxic β-amyloid.

"So BACE1 is a double whammy when it comes to memory," Xu said. "But that also means that a therapy that targets BACE1 could be a double punch against , and even just normal aging-related . That's why we're now looking for ways to block BACE1 expression in the brain."

Explore further: New drug target improves memory in mouse model of Alzheimer's disease

Related Stories

New drug target improves memory in mouse model of Alzheimer's disease

March 7, 2012
(Medical Xpress) -- Researchers at the University of California, San Diego, the Medical University of South Carolina, the University of Cincinnati, and American Life Science Pharmaceuticals of San Diego have validated the ...

Impaired energy metabolism linked with initiation of plaques in Alzheimer's brain

December 24, 2008
Scientists have identified an initiating molecular mechanism in sporadic Alzheimer's disease (AD). The study, published by Cell Press in the December 26th issue of the journal Neuron, provides new information about generation ...

Potential new drug candidate found for Alzheimer's disease

May 31, 2011
Researchers at the University of California, San Diego, the Medical University of South Carolina and American Life Science Pharmaceuticals of San Diego have demonstrated that oral administration of a cysteine protease inhibitor, ...

Poor recycling of BACE1 enzyme could promote Alzheimer's disease

November 21, 2011
Sluggish recycling of a protein-slicing enzyme could promote Alzheimer's disease, according to a study published online on November 21 in The Journal of Cell Biology.

Researchers discover new link to schizophrenia

May 8, 2008
Neuroscientists at Johns Hopkins have discovered that mice lacking an enzyme that contributes to Alzheimer disease exhibit a number of schizophrenia-like behaviors. The finding raises the possibility that this enzyme may ...

Diametric shift in 2 protein levels spurs Alzheimer's plaque accumulation

December 1, 2011
A diametric shift in the levels of two proteins involved in folding, moving and cutting other proteins enables accumulation of the destructive brain plaque found in Alzheimer's disease, researchers report.

Recommended for you

Meditation and music may alter blood markers of cellular aging and Alzheimer's disease

November 13, 2018
A research team led by Dr. Kim Innes, a professor in the West Virginia University School of Public Health, has found that a simple meditation or music listening program may alter certain biomarkers of cellular aging and Alzheimer's ...

Alzheimer's and cardiovascular disease share common genetics in some patients

November 9, 2018
Genetics may predispose some people to both Alzheimer's disease and high levels of blood lipids such as cholesterol, a common feature of cardiovascular disease, according to a new study by an international team of researchers ...

Artificial intelligence predicts Alzheimer's years before diagnosis

November 6, 2018
Artificial intelligence (AI) technology improves the ability of brain imaging to predict Alzheimer's disease, according to a study published in the journal Radiology.

Diabetes medications may reduce Alzheimer's disease severity

November 1, 2018
People with Alzheimer's disease who were treated with diabetes drugs showed considerably fewer markers of the disease—including abnormal microvasculature and disregulated gene expressions—in their brains compared to Alzheimer's ...

Massive study confirms that loneliness increases risk of dementia

October 29, 2018
A new Florida State University College of Medicine study involving data from 12,000 participants collected over 10 years confirms the heavy toll that loneliness can take on your health: It increases your risk of dementia ...

Bioactive compound from the Rhodiola plant improves memory

October 25, 2018
In an ageing society, more people are suffering from memory disorders. The progressive loss of memory severely impairs the quality of life of those affected. So far, no drugs are known to prevent age-related cognitive decline.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.