One of Alzheimer’s disease’s key players, beta-amyloid presents a complex picture: “Every patient with Alzheimer’s disease has amyloid plaque in his or her brain. But, not everyone with amyloid plaque in the brain has Alzheimer’s disease. How’s that for complications?” –Cassava CEO Remi Barbier
If you or a loved one is going through the diagnostic process for Alzheimer’s, one of the terms you’re likely to hear quite a bit is beta-amyloid. Because this protein is found aggregating in clumps in the brains of people with Alzheimer’s, it is considered one of the disease’s key biomarkers.
By identifying it in a patient’s brain, physicians have one piece of the puzzle to contribute to the overall picture. Here’s what you need to know about what beta-amyloid is, its role in neurodegeneration, how it’s detected, and how it can be treated.
The Alzheimer’s Hallmark
When diagnosing Alzheimer’s Disease, researchers have looked at the brain for plaque deposits of the beta-amyloid peptide — a collection of the amino acid molecules that make up a protein. Beta-amyloid peptides build up to form beta-amyloid plaques that clog up the brains of Alzheimer’s patients. This is linked to neurodegenerative changes that many scientists believe are the early phases of Alzheimer’s.
While researchers have yet to completely understand the exact way that beta-amyloid operates, there are theories that early on, smaller clumps of beta-amyloid oligomers — or proteins — lead to cognitive impairment and, down the road, Alzheimer’s.
That puts beta-amyloid front and center in the “amyloid hypothesis,” a working theory that beta-amyloid gums up the works, disrupting the brain’s connectivity, leading to cell death in certain key regions of the brain, and causing Alzheimer’s dementia. Studies have not succeeded in determining the exact role beta-amyloid plays in the disease, but one line of thinking is that early on, beta-amyloid sets off a domino effect. Once started, the brain’s degeneration is progressive, attacking region by region.
At this point, diagnoses for Alzheimer’s are still limited and, with that, often inaccurate.
The most definitive tests include searching for amyloid plaques post-mortem, in the brains of suspected Alzheimer’s patients. But there are a few other tools available in a clinical setting: For starters, diagnostic methods include MRI imaging of the brain, which helps to rule out other conditions, and can help point to brain changes that provide clues about Alzheimer’s, like revealing areas of brain atrophy, which is associated with plaque presence. This is particularly useful when scanning particular regions of the brain that are most often impacted by Alzheimer’s, such as the medial lobe.
For more definitive results, currently a patient needs to get an amyloid PET scan (which stands for positron emission tomography) to reveal a helpful picture of amyloid plaques in the brain, or a lumbar puncture (also known as a spinal tap) to help clinicians look for biomarkers in cerebrospinal fluid, like amyloid and tau protein. These tests are generally standard for people who are, for example, participating in clinical trials for Alzheimer’s treatments.
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However, only a small percentage of people ultimately have access to PET scans: They may be hard to come by, especially away from major cities and big hospitals, and on top of that, they are expensive and not typically covered by insurance. To solve for this inaccessibility, diagnostic companies are racing to find alternative solutions, like using just a quick blood draw to reveal more concrete evidence.
New diagnostic technologies that look for Alzheimer’s biomarkers like beta-amyloid are in development, including retinal scans and blood tests, and AI-powered diagnostic tools, including a virtual microscope. In December of 2020, the very first blood test for Alzheimer’s became commercially available, for around $1,250. However, it has yet to secure FDA approval.
Going After Beta-amyloid
Guided by the amyloid hypothesis, many of the drug treatment efforts have targeted beta-amyloid plaques. The recent FDA approval of Aduhelm, in fact, is the result of this research. It is not without controversy, however.
While no one questions the fact that the drug can successfully remove these amyloid deposits, critics argue the effectiveness of that approach. While some people who took part in the Aduhelm clinical trials have said they suspected that the drug helped them feel clearer-headed or kept their Alzheimer’s symptoms at bay, efficacy data from the trial was, by many accounts, unconvincing.
“This is a double-edged sword,” Dr. Lon Schneider, director of the California Alzheimer’s Disease Center at USC told Being Patient, ”By approving the medication on the basis of a change in the biomarker, the FDA has essentially elevated that biomarker — the amyloid in general — to a premier place, to a major place.”
Indeed, anti-amyloid drugs like Aduhelm have a long history of failed trials. As such, researchers are looking at other avenues for drug development too, such as treatments that target tau proteins and inflammation. So far, there is no “magic bullet” for treating Alzheimer’s, and that may well be the case in the future, too. Instead, some experts say the disease, which affects different people in different ways, will require a multi-pronged drug approach.
No matter what, beta-amyloid will continue to play a key role in how doctors identify and potentially treat Alzheimer’s patients. Understanding its place in the complex Alzheimer’s picture will continue as an area of focus for a long time to come.