Advancing the search for antibodies to treat Alzheimer's disease

July 30, 2018, Brigham and Women's Hospital
Diagram of the brain of a person with Alzheimer's Disease. Credit: Wikipedia/public domain.

Two new studies published by investigators from Brigham and Women's Hospital illustrate that not all forms of amyloid-beta (Aβ) protein—the protein thought to initiate Alzheimer's disease—play an equally menacing role in the progress of the disease. Using a new way of preparing and extracting the protein as well as a new technique to search for promising drug candidates, researchers have highlighted the importance of testing and targeting different forms of Aβ. Their work may help advance the search for more precise and effective drugs to prevent or halt the progress of Alzheimer's disease.

"Many different efforts are currently underway to find treatments for Alzheimer's disease, and anti-Aβ antibodies are currently the furthest advanced. But the question remains: what are the most important forms of Aβ to target? Our study points to some interesting answers," said Dominic Walsh, Ph.D., a principal investigator in the Ann Romney Center.

Aβ protein can take forms ranging from monomers—single molecules—to twisted tangles of plaques that can pollute the brain and are large enough that they can be seen with a traditional microscope. Walsh compares monomers to single Lego bricks, which can start sticking together to form complex structures of varying sizes. The two recently published studies investigate how to find new potential therapeutics that can target the structures most likely to cause harm.

Most Alzheimer's disease studies use synthetic Aβ to approximate what conditions in the brain of an Alzheimer's patient might be like. A small number of researchers have used Aβ extracted from human brain, but the extraction process is crude. In a study published in Acta Neuropathologica in April, Walsh and colleagues developed a much gentler extraction protocol to prepare samples from subjects with Alzheimer's disease. The team found that Aβ was far more abundant in traditional crude extracts, but that the bulk of the extracted Aβ was innocuous. In contrast, much less Aβ was obtained with the gentler protocol, but in this case most of the Aβ was toxic.

In a second study published in Nature Communications in July, Walsh and colleagues developed a screening test to try to find potential drugs to target the toxic forms of Aβ. The uses extracts of brain samples from Alzheimer's disease patients and live-cell imaging of stem-cell derived cells to find promising therapeutics. The team reports on 1C22, an Aβ antibody that they found could protect against toxic forms of amyloid-beta more effectively than the most clinically advanced Alzheimer's therapeutics currently in clinical trials.

"We anticipate that this primary screening technique will be useful in the search to identify more potent anti-Aβ therapeutics in the future," said Walsh.

Explore further: Brain cholesterol associated with increased risk of Alzheimer's disease

More information: Ming Jin et al, An in vitro paradigm to assess potential anti-Aβ antibodies for Alzheimer's disease, Nature Communications (2018). DOI: 10.1038/s41467-018-05068-w

Related Stories

Brain cholesterol associated with increased risk of Alzheimer's disease

May 7, 2018
Researchers have shown how cholesterol—a molecule normally linked with cardiovascular diseases—may also play an important role in the onset and progression of Alzheimer's disease.

Can aspirin treat Alzheimer's?

July 2, 2018
A regimen of low-dose aspirin potentially may reduce plaques in the brain, which will reduce Alzheimer's disease pathology and protect memory, according to neurological researchers at Rush University Medical Center, who published ...

Can nanotechnology help treat Alzheimer's?

June 19, 2018
Alzheimer's disease (AD) is the most common form of dementia. It takes a devastating toll on patients and family members, who are usually the caregivers. Current drugs only treat symptoms of AD, not its causes.

Alzheimer's drug targeting soluble amyloid falls short in a large clinical trial

January 25, 2018
A paper published today in the New England Journal of Medicine reports that solanezumab, a monoclonal antibody-based treatment for Alzheimer's disease developed by Eli Lilly that targets amyloid plaques, did not significantly ...

Antibody removes Alzheimer's plaques, in mice

March 26, 2018
Years before people start showing characteristic symptoms of Alzheimer's disease, sticky plaques begin forming in their brains, damaging nearby cells. For decades, doctors have sought ways to clear out these plaques as a ...

Blood-based marker for Alzheimer's disease shows diagnostic potential

February 2, 2018
Researchers in Japan and Australia have used the ratio of different forms of the hallmark Alzheimer's protein, amyloid, in blood to detect those who have high levels of the protein in their brain. Their findings are published ...

Recommended for you

Researchers classify Alzheimer's patients in six subgroups

December 5, 2018
Researchers studying Alzheimer's disease have created an approach to classify patients with Alzheimer's disease, a finding that may open the door for personalized treatments.

Neuroscientists pinpoint genes tied to dementia

December 3, 2018
A UCLA-led research team has identified genetic processes involved in the neurodegeneration that occurs in dementia—an important step on the path toward developing therapies that could slow or halt the course of the disease. ...

Detecting signs of neurodegeneration earlier and more accurately

November 30, 2018
Signs of neurodegenerative diseases, appearing years before the emergence of clinical manifestations, can be detected during the examination of medical samples by means of fluorescence microscopy by using new sensitive and ...

Never-before-seen DNA recombination in the brain linked to Alzheimer's disease

November 21, 2018
Scientists from Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified gene recombination in neurons that produces thousands of new gene variants within Alzheimer's disease brains. The study, published today ...

New information on the pathological mechanisms of Alzheimer's disease

November 21, 2018
Researchers at the University of Helsinki have discovered a mechanism by which harmful tau protein aggregates are transmitted between neurons. Alongside amyloid plaques, tau aggregates in the brain are a significant factor ...

DNA vaccine reduces both toxic proteins linked to Alzheimer's

November 20, 2018
A DNA vaccine tested in mice reduces accumulation of both types of toxic proteins associated with Alzheimer's disease, according to research that scientists say may pave the way to a clinical trial.

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.