Insights into Amyloid Natural State Suggest New Course of Alzheimer’s Treatment

Insights into Amyloid Natural State Suggest New Course of Alzheimer’s Treatment

With the help of an extremely powerful infrared spectroscopy method, researchers have found evidence challenging the widely held theory that Alzheimer’s disease can be prevented by clearing amyloid-beta from the brain.

The research team at Lund University in Sweden discovered that amyloid-beta naturally exists as a four-unit complex and not as a single peptide (a shorter protein) as researchers believe. This suggests that it may be the separation of the complex’s smaller pieces that makes amyloid aggregate.

Therefore, the team suggests that it may be possible to treat Alzheimer’s by using drugs that stabilize the amyloid complex. Such a drug is already approved for a disease caused by the breaking up of a four-unit amyloid-complex.

The study, “Pre-plaque conformational changes in Alzheimer’s disease-linked Aβ and APP,” was published in the journal Nature Communications.

“No one has used this method to look at Alzheimer’s development before. The images tell us that the progression is slower than we thought and that there are steps in the development of Alzheimer’s disease that we know little about. This, of course, sparked our curiosity,” Gunnar Gouras, professor in experimental neurology at Lund University and senior author of the study, said in a press release.

Today, the scientific community is dominated by a number of ideas. Many researchers are convinced that Alzheimer’s disease is linked to the development of amyloid-beta plaque — which has led to numerous clinical trials of drugs trying to treat the disease by clearing plaque. So far, all have failed.

Another idea is that amyloid occurs naturally as a single peptide, and that once it starts aggregating, the processes swiftly lead to plaque formation.

But although the ideas are embraced by many, they have been difficult to prove. Current methods to process brain tissue to study the structure of amyloid can introduce changes in the structure and composition of amyloid aggregates.

In addition to the powerful imaging, the team used other methods, such as antibodies that only bind amyloid in specific three-dimensional shapes, to reach their conclusions.

They discovered that amyloid is naturally present as a tetramer — a complex formed by four amyloid-beta peptides. This discovery made the team realize that it may have found an entirely new explanation for Alzheimer’s development.

It could be that, as the complex breaks up, the amyloid parts start behaving in an unstable manner, ultimately forming plaque. The team’s research also showed that plaque formation happened at a much slower rate than previously thought.

“This is very, very exciting. In another amyloid disease, transthyretin amyloidosis, the breaking up of the tetramer has been identified as key in disease development,” Gouras said. “For this disease, there is already a drug in the clinic that stabilizes the tetramers, consequently slowing down disease progression. We hope that stabilizing beta-amyloid in a similar fashion may be the way forward in developing future therapies.”

The team is now working to better understand how the amyloid peptides interact. They believe that if they identified the factor leading to the breakdown of the four-unit complex, it could shift the course of treatment development in Alzheimer’s disease.

3 comments

  1. Linda Grishman says:

    I have early stage Alzheimer’s. It runs on my maternal side. My aunt, my Mom my Aunts daughter and my sister. All are deceased. My sister was 12 years older than I.
    Being extremely concerned that I may get the disease, I saw a number of neurologists in NYC. I live in Burlington VT.
    To cut a long story short, I have been on Aricept 10mg for several years. I also suffer from depression and have been on a cocktail of drugs for many many years.

    I am 67 and in good health except for short term memory problems. I live alone with my 3 cats in Burlington VT.

    I would be very appreciative if you could send me detailed information. I will do anything to stop this disease in its tracks. I hope to hear from you.

    Linda Grishman
    Burlington VT

    • Magdalena Kegel says:

      Dear Linda,
      Thank you for sharing your story. We at Alzheimer’s News Today are truly sorry to hear that you are anticipating the disease.
      The best way to keep updated is to sign up for our newsletter, where we frequently include information about clinical trials. many trials now focus on patients who do not yet have diagnosed Alzheimer’s disease, but are at risk of developing the illness.

  2. Roger Mayes says:

    The article references a drug already approved for other purposes may be helpful to AD patients by breaking up the amyloid complex. The article does not mention the name of this approved drug. My wife was in the Merck clinical trial of MK8931 for 4 years. Merck recently “pulled the plug on the trial because it became clear that the drug had little chance of approval. Some believe the trial was targeting the wrong profile. My wife stabalized trememdously during the trial, therefore I am convinced that the drug did help her. Now I am searching for a new trial (thru Trial Match) or a new treatment. It seems to me that we are on the cutting edge of finding help but time is not on Marilyn’s side. Also FYI, she has been on elevated doses of Airicept and Namenda for many years.
    Any insight for a direction would be appreciated.

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