ReviewFrontiers in aging neuroscience2018
Can an Infection Hypothesis Explain the Beta Amyloid Hypothesis of Alzheimer's Disease?
Review in Frontiers in aging neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 5 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
118 citing papers in PubMed, 5 syntheses or guidelines pooled it, 193 citations in OpenAlex.
- Safety and efficacy of lecanemab for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials.Frontiers in aging neuroscience · 2023Pooled it
- Is Periodontitis Associated with Age-Related Cognitive Impairment? The Systematic Review, Confounders Assessment and Meta-Analysis of Clinical Studies.International journal of molecular sciences · 2022Pooled it
- Risk of Dementia or Cognitive Impairment in Sepsis Survivals: A Systematic Review and Meta-Analysis.Frontiers in aging neuroscience · 2022Pooled it
- Pooled it
- Common Bacterial Infections and Risk of Dementia or Cognitive Decline: A Systematic Review.Journal of Alzheimer's disease : JAD · 2020Pooled it
- Pathological or preventative? Amyloid-β as an effector of innate immunity.Infection and immunity · 2026Review
- Long-term risk of dementia following encephalitis: a large-scale retrospective cohort study of electronic health records.Journal of neurology · 2026Article
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- A mechanistic framework linking the oral microbiome to Alzheimer's disease through neuroinflammation.Journal of Alzheimer's disease : JAD · 2026Review
- High reelin expression may explain why a subgroup of entorhinal cortex neurons functions as an initial nucleation site of Alzheimer's disease.PLoS computational biology · 2026Article
- Convergence of neuroinflammation across major neurotropic viral exposomes in AD and ADRD.Journal of neuroinflammation · 2026Review
- Role of Microbial Toxins in Neurodegenerative Diseases: Insights and Future Perspectives.Biomolecules · 2026Review
- Unmasking the hidden catalyst: How infections trigger Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Review
- The dysregulation of innate immunity by Porphyromonas gingivalis in the etiology of Alzheimer's disease.Journal of internal medicine · 2026Review
- Infection trajectories and dementia risk in type 2 diabetes.Diabetology & metabolic syndrome · 2026Article
- The triple-hit hypothesis of Alzheimer's disease: blood-brain barrier breakdown, infection, and neuroimmune activation as a unified etiological framework.Frontiers in neuroscience · 2026Article
- Association between environmental mold exposure and mild cognitive impairment in older adults: a case-control study.Frontiers in public health · 2026Article
- Therapeutic Potential ofLife (Basel, Switzerland) · 2025Review
- Modulation of AβJournal of chemical information and modeling · 2025Article
- Helicobacter hepaticus CdtB promoted brain impairment in BALB/c mice via gut-brain axis.Gut pathogens · 2025Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is the most frequent type of dementia. The pathological hallmarks of the disease are extracellular senile plaques composed of beta-amyloid peptide (Aβ) and intracellular neurofibrillary tangles composed of pTau. These findings led to the "beta-amyloid hypothesis" that proposes that Aβ is the major cause of AD. Clinical trials targeting Aβ in the brain have mostly failed, whether they attempted to decrease Aβ production by BACE inhibitors or by antibodies. These failures suggest a need to find new hypotheses to explain AD pathogenesis and generate new targets for intervention to prevent and treat the disease. Many years ago, the "infection hypothesis" was proposed, but received little attention. However, the recent discovery that Aβ is an antimicrobial peptide (AMP) acting against bacteria, fungi, and viruses gives increased credence to an infection hypothesis in the etiology of AD. We and others have shown that microbial infection increases the synthesis of this AMP. Here, we propose that the production of Aβ as an AMP will be beneficial on first microbial challenge but will become progressively detrimental as the infection becomes chronic and reactivates from time to time. Furthermore, we propose that host measures to remove excess Aβ decrease over time due to microglial senescence and microbial biofilm formation. We propose that this biofilm aggregates with Aβ to form the plaques in the brain of AD patients. In this review, we will develop this connection between Infection - Aβ - AD and discuss future possible treatments based on this paradigm.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.