This New Approach to Alzheimer’s Treatment will Surprise You

As we all know, the human body can have flaws– many of which are the result of imperfect cellular processes. These mistakes sometimes prove to be harmless, but in some instances they produce disease or even death.

Alzheimer’s disease is the result of a cellular processing flaw that occurs when the amyloid precursor protein (APP) is severed in the incorrect spot along the neuron membrane. This causes a buildup of abnormal fragments we call amyloid-beta. The fragments slowly begin to clump together and eventually form a plaque that surrounds the neurons and interferes with normal brain functions.

Fortunately, human cells have evolved several systems that can safeguard against such a disaster. Retromer is this protein complex that is essentially a microscopic garbage truck. The retromer goes around collecting flawed gene products and bustling them off to be recycled or destroyed.

A Different Direction for Alzheimer’s Research

The bulk of Alzheimer’s research has looked for better ways to prevent the formation of amyloid-beta without bearing much fruit. So what would happen if clinical investigators decided to take a markedly different approach? What if they looked into improving the cellular defense systems that are already in place?

This is exactly what a collaborative team of researchers from the Columbia University Medical Center (CUMC), Brandeis University and Weill Cornell Medical College did. They have developed a totally new approach to treating Alzheimer’s disease. This therapy not only significantly boosts retromer levels, but also reduces amyloid-beta levels in neurons without any collateral damage to the cell itself.

Two of the leading investgators for this Alzheimer’s clinical research were Gregory Petsko, the former professor of biochemistry and chemistry at Brandeis, and Dagmar Ringe, the Harold and Bernice Davis Professor in the Departments of Biochemistry and Chemistry. Their research has been published in the journal Nature Chemical Biology.

Prior studies have shown that Alzheimer affected brains possess less retromer. The research team reasoned that increasing retromer levels in the neurons would decrease amyloid-beta levels. Up until now, researchers were unable to devise an efficient method of pharmacologically strengthening the retromer complex.

We Needed Pharmacological Chaperones

The key to the success of this Alzheimer’s disease clinical trial was the discovery of compounds known as pharmacological chaperones. These compounds actually bind to the weak points in the retromer and effectively reinforce it. The more resilient retromer has a much easier time moving the amyloid-beta.

The research team used a particular chaperone (known as R55) for this study that could be attached to the neurons in the cell cultures. R55 reinforced the retromer just as an improved engine reinforces the strength of a dilapidated garbage truck. The results were nearly instantaneous— retromer levels increased and amyloid-beta levels decreased.

(Quick Fact: This research team has only tested the effects of R55 on lab mice so far.)

It should be noted that this does not represent a cure for Alzheimer’s disease, only a better method of prevention and treatment. This type of therapy would not be able to halt the disease’s progress once it has been diagnosed.

However, it can be used to slow down its progression, this ALZ research represents a very important step forward. This clinical trial was funded by organizations like the Alzheimer’s Association and the National Institutes of Health.