Research Spotlight: Amylin and Amyloid-Beta Synergize Against Microbes and May Not Be Mere Disease Byproducts

Deepak Vijaya Kumar, PhD, and Rudolph Tanzi, PhD, both of the department of neurology at Massachusetts General Hospital, published a paper in Alzheimer’s & Dementia, “Human amylin is a potent antimicrobial peptide that exhibits antimicrobial synergism with the amyloid-β protein.”

Q: How would you summarize your study for a lay audience?

Our team discovered that amylin—a hormone linked to type 2 diabetes—has strong germ-fighting abilities. When teamed up with amyloid-beta, a protein associated with Alzheimer’s disease (AD), it forms sticky fibrils that trap and neutralize harmful microbes.

Using brain cell models and tiny worms called C. elegans, we showed that these proteins may be part of the body’s natural immune defense.

What’s often seen as harmful buildup in diseases like Alzheimer’s and diabetes might actually begin as a protective response that goes off track over time.

This opens up new ways to understand and potentially treat these conditions.

Q: What question(s) were you investigating?

We wanted to know if amylin and amyloid-beta play a helpful role in the immune system. Specifically, we asked whether their tendency to clump—usually seen as harmful—could actually help trap and fight microbes.

This led us to a bigger question: could the protein buildup seen in Alzheimer’s and diabetes start as a natural defense that later becomes problematic?

Q: What methods or approach did you use?

To explore this, we used:

1. Lab tests to measure germ-killing ability (e.g., MIC and time-kill tests)
2. Electron microscopy to visualize how the proteins trap microbes
3. Cell and worm models to study real-life interactions
4. 3D brain-like cultures to mimic Alzheimer’s conditions
5. Protein tracking tools such as ELISA and immunogold microscopy
6. Brain tissue analysis from Alzheimer’s patients to see if proteins and microbes appear together

Q: What did you find?

We found that human amylin can kill various bacteria and fungi, either by attacking them directly or trapping them in sticky fibrils. It worked even better when combined with amyloid-beta.

Together, they demonstrated greater effectiveness in combating resilient microbes like Salmonella Typhimurium and Staphylococcus aureus than when used individually.

In lab-grown brain cells, infections triggered the release of amylin, and both proteins formed clumps that helped neutralize the invaders.

Q: What are the implications?

These findings suggest that amylin and amyloid-beta might be part of the body’s natural defense system—not just harmful byproducts of disease.

This shifts how we think about Alzheimer’s and diabetes. If we can support their protective role without causing harmful buildup, it could lead to better treatments and earlier ways to detect and prevent these diseases.

Q: What are the next steps?

Future work will focus on:

1. Testing how amylin and amyloid-beta work together in live animal models, especially in cases of infection and neurodegenerative diseases.
2. Studying the molecular interactions between amylin and amyloid-beta during immune responses.
3. Identifying the range of microbes that trigger this protein synergy.
4. Understanding whether adjusting the levels of amylin or amyloid-beta can offer therapeutic benefits without causing harmful buildup.
5. Studying the timing of infection, immune activation, and protein accumulation in models of Alzheimer’s disease and type 2 diabetes to better understand how these processes are linked.

Authorship: In addition to Drs. Kumar and Tanzi, Mass General Brigham authors include Teryn A. Mitchell, Breeya A. Tailor, Alexander P. Moir, Nanda K. Navalpur Shanmugam, William A. Eimer, Jessica Ghelichi, Se Hoon Choi, Chienwen Su, Alex S. Rodriguez, Eunhee Kim, Robert D. Moir

Paper cited: Vijaya Kumar, D. K., et al. “Human amylin is a potent antimicrobial peptide that exhibits antimicrobial synergism with the amyloid-β protein.” Alzheimer’s & Dementia. DOI: 10.1002/alz.70490

Funding: This work was supported by grants by grants from the National Institutes of Health (1S10RR023594S10), the Dake Family Foundation and the Cure Alzheimer’s Fund

Disclosures: The authors declare no competing financial or commercial interests. The study was supported by nonprofit and federal funding sources. All experimental procedures complied with institutional and ethical standards.