Low levels of brain protein may lead to Alzheimer's

Feb 15, 2011

In Alzheimer’s disease, short, toxic amyloid beta peptides build up inside the brain, erasing memories, altering behavior, and ultimately destroying lives.

Scientists have a good idea how toxic amyloid beta is created, but what’s not clear is why excessive amounts of amyloid beta accumulate in people who develop Alzheimer’s. After all, each of us produces some degree of the toxic protein throughout our lives.

Now findings suggest that amyloid beta may accumulate in some patients because of a flaw in their neurons’ internal transportation system, according to a new study from researchers in the Taub Institute at Columbia University College of Physicians and Surgeons and the University of Toronto. The study was led by Christiane Reitz, MD, assistant professor of neurology, and Richard Mayeux, MD, the Sergievsky Professor of Neurology, Psychiatry, and Epidemiology and co-director of the Taub Institute of Research on and the Aging Brain at P&S, and was published in the Jan. issue of the .

Like all cells, neurons use transport proteins to ship cellular components from one region of the cell to another. The shipping process is critical to the production of amyloid beta: transport proteins must carry the amyloid precursor protein (APP) to certain regions of the cell where the protein is processed into soluble forms of amyloid beta.

The new research reveals that a different transport protein, called SORCS1, appears to ferry APP to safe destinations within the cell where it’s sliced into non-toxic pieces instead of amyloid beta.

Alzheimer’s patients appear to express reduced levels of SORCS1 in their brains, Reitz and Mayeux also found, suggesting that APP in patients is more likely to be shipped to cellular compartments that process the protein into toxic amyloid.

Genetic studies included in the paper also show that people who carry certain variants of the SORCS1 gene have a 15 percent greater risk of developing Alzheimer’s.
Taken together, Mayeux says the results show that APP transport proteins are key players in the development of Alzheimer’s disease, especially when considered with similar findings for a related transport protein called SORL1. (The same Columbia and Toronto research group discovered the SORL1 link four years ago).

Increasing SORCS1 or SORL1 activity could potentially reduce the amount of amyloid beta in the and slow or prevent Alzheimer’s. SORCS1 and SORL1 may be hard to target directly, but other proteins in the SORCS1-SORL1 network could provide better opportunities, Mayeux says.

The researchers are now collaborating with Columbia’s Initiative in Systems Biology 
and Center for the Multiscale Analysis of Genetic Networks to map the entire network and identify promising targets.

Explore further: REM sleep critical for young brain development; medication interferes

Related Stories

Development of a safer vaccine for Alzheimer’s disease

Nov 17, 2010

A new vaccine protects against memory problems associated with Alzheimer's disease, but without potentially dangerous side effects, a new animal study reports. The research was presented at Neuroscience 2010, the annual meeting ...

Alzheimer's prevention role discovered for prions

Jul 03, 2007

A role for prion proteins, the much debated agents of mad cow disease and vCJD, has been identified. It appears that the normal prions produced by the body help to prevent the plaques that build up in the brain to cause Alzheimer’s ...

New approach to Alzheimer's therapy

Jul 30, 2010

Researchers from the German Centre for Neurodegenerative Diseases and the Ludwig-Maximilians-Universitat in Munich have shown that the ADAM10 protein can inhibit the formation of beta-amyloid, which is responsible for Alzheimer's ...

Recommended for you

Making waves with groundbreaking brain research

10 hours ago

New research by Jason Gallivan and Randy Flanagan suggests that when deciding which of several possible actions to perform, the human brain plans multiple actions simultaneously prior to selecting one of ...

Long-term memories are maintained by prion-like proteins

Jul 02, 2015

Research from Eric Kandel's lab at Columbia University Medical Center (CUMC) has uncovered further evidence of a system in the brain that persistently maintains memories for long periods of time. And paradoxically, ...

Water to understand the brain

Jul 02, 2015

To observe the brain in action, scientists and physicians use imaging techniques, among which functional magnetic resonance imaging (fMRI) is the best known. These techniques are not based on direct observations ...

User comments : 0

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.