HYPOTHESIS AND THEORY article
Front. Cell. Infect. Microbiol.
Sec. Extra-intestinal Microbiome
This article is part of the Research TopicThe brain pathobiome in Alzheimer's disease and other neurodegenerative diseasesView all articles
The Amyloid-Beta Wave Hypothesis of Alzheimer's Disease
Provisionally accepted
- 1Yale School of Medicine, New Haven, United States
- 2Endicott College, Beverly, United States
- 3Massachusetts General Hospital, Boston, United States
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Alzheimer's disease (AD) is a complex and multifactorial disorder that affects all races and genders. Genetic traits influenced by lifestyle and environment lead to a tremendous amount of heterogeneity in Alzheimer's disease onset and severity. Regardless of these unique contributing factors, Alzheimer's disease is traditionally met with amyloid-beta plaque formation in the central nervous system. In this commentary, we shed light on the growing literature surrounding amyloid-beta's ability to act as an antimicrobial peptide in the central nervous system's innate immune response to pathogenic infections. We hypothesize that there are, "amyloid-beta waves" that are created by the responses of neuroglia and neurons to microbial pathogens. The improper clearance and residual buildup of amyloid-beta waves throughout life increases the likelihood of developing Alzheimer's disease. In conclusion, we suggest that anti-amyloid therapies during pathogenic infections or flare-ups may slow the development of Alzheimer's disease by reducing amyloid-beta waves throughout the aging of individuals.
Keywords: amyloid-beta, microbial infections, Alzheimer's disease, Aging, etiology, antimicrobialpeptide
Received: 11 Oct 2025; Accepted: 07 Nov 2025.
Copyright: © 2025 Miller, Logan, Hafler and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sean James Miller, sean.miller@yale.edu
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