'More potent' Alzheimer's therapy is on its way

Individuals with Alzheimer's disease are increasingly affected by memory loss, disorientation, and impaired decision-making. There are currently no cures for this condition, but researchers are taking steps to tackle some of its physiological sources in the brain.

Alzheimer's disease is characterized by the formation of amyloid plaques in the brain, which interfere with the normal communication flow between brain cells. These plaques are made out of beta-amyloid amino acids that stick together.

Over the past few years, researchers from various institutions have been working to develop antibodies — a type of protein harnessed by the immune system as part of the immune response — able to interfere with beta-amyloid and prevent the formation of plaques in the brain.

But the search for effective antibodies, though promising, has been riddled with obstacles and setbacks. That is why a team of researchers from Brigham and Women's Hospital in Boston, MA, has recently conducted a series of experiments to identify a better way of targeting beta-amyloid.

This, they hoped, would lead to the development of a more efficient antibody to be used in Alzheimer's therapy.

Principal investigator Dominic Walsh and team came up with a novel technique to collect beta-amyloid and to prepare it in the laboratory.

Beta-amyloid: Which forms are toxic?

"Many different efforts are currently underway to find treatments for Alzheimer's disease, and anti-[beta-amyloid] antibodies are currently the furthest advanced," says Walsh.

"But the question remains: what are the most important forms of [beta-amyloid] to target?"

"Our study points to some interesting answers," the lead researcher adds, and these answers are now reported in an open access paper published in the journal Nature Communications.

As the researchers explain, beta-amyloid can be found in many forms. At one end of the spectrum, there is the monomer (a type of molecule), which is not necessarily toxic.

At the other end, there is the beta-amyloid plaque, in which molecules become tangled together. Beta-amyloid plaques are large enough to be observed using a traditional microscope, and they are involved in the development of Alzheimer's.

In the current study, as well as in a previous one, Walsh and team have looked at beta-amyloid structures, in an effort to identify the ones that are most harmful in the brain. In doing so, they believed they would be able to develop an antibody capable of specifically targeting those toxic amino acids.

Better techniques, more effective therapy

The researchers note that, typically, specialists use synthetic beta-amyloid samples to create a laboratory model of Alzheimer's disease in the brain. Very few scientists, Walsh and team note, collect beta-amyloid from the brains of individuals diagnosed with the disease.

So far, beta-amyloid extraction techniques have been crude, so Walsh and his colleagues decided to try and perfect the extraction protocol. They did this in a recent study published a few months ago, in the journal Acta Neuropathologica.

In the earlier study, the researchers noticed that beta-amyloid was sourced more abundantly using the crude extraction protocol; however, the samples tended to yield non-toxic amino acids.

By employing their newly developed, gentler technique of extraction, the team secured less beta-amyloid, but most of it proved to be toxic — just the kind of beta-amyloid the researchers were interested in targeting, to come up with better treatments for Alzheimer's disease.

In the current study, Walsh and team focused on finding better drugs to target toxic beta-amyloid. To do so, they developed a novel screening test that requires extracting brain samples from people with Alzheimer's, as well as live-cell imaging — which allows scientist to monitor living cells — of neurons obtained from stem cells.

This screening test allowed the team to discover a particular antibody — called "1C22" — that is able to tackle toxic forms of beta-amyloid more effectively than other antibodies currently being tested in clinical trials.

"We anticipate that this primary screening technique will be useful in the search to identify more potent anti-[beta-amyloid] therapeutics in the future," Walsh notes.