New developments in Alzheimer’s research are bringing us closer to more precise therapies for this debilitating disease.
Alzheimer’s disease, is characterized by the formation of amyloid plaques in the brain, which interfere with the normal communication flow between brain cells, leading to debilitating symptoms like memory loss and impaired decision-making. These plaques are made out of beta-amyloid proteins that stick together.
Over the past few years, researchers from several institutions have been working to develop antibodies that bind to and neutralize the toxic effects of the beta-amyloid. The search for effective antibodies, although promising, has been riddled with setbacks. Knowing this, a team of researchers from Brigham and Women’s Hospital in Boston, MA, decided to approach this issue from a different angle – by conducting experiments to identify a better way of targeting beta-amyloid. Their goal was to develop 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.
“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.”
Beta-amyloid can be found in many forms. At one end of the spectrum, it exists as a single protein, or monomer, which isn’t necessarily toxic.
At the other end, there is the beta-amyloid plaque, in which many beta-amyloid proteins 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 looked at beta-amyloid structures to identify the ones that are most harmful in the brain.
Typically specialists use synthetic beta-amyloid samples to create a laboratory model of Alzheimer’s disease in the brain. Very few scientists actually collect beta-amyloid from the brains of individuals diagnosed with the disease.
In the current study, Walsh and team focused on finding better a more specific antibody to target the toxic forms of beta-amyloid but not the less harmful forms. To do so, they developed a novel screening test that requires extracting beta-amyloid from brain samples from people with Alzheimer’s. They added these extracts to induced pluripotent stem cell-derived human neurons and observed the ability of the different antibodies to block the toxic effects of the beta-amyloid.
This screening test allowed the team to discover a particular antibody — called “1C22” — that is able to block toxic forms of beta-amyloid more effectively than other antibodies currently being tested in clinical trials.
Walsh explained the implications of their novel screening method:
“We anticipate that this primary screening technique will be useful in the search to identify more potent anti-[beta-amyloid] therapeutics in the future.”