A reappraisal on amyloid cascade hypothesis: The role of chronic infection in Alzheimer’s disease
Abstract
Alzheimer disease (AD) is a progressive neurological disorder that accounted for the most common cause of dementia in the elderly population. Lately, ‘infection hypothesis’ has been proposed where the infection of microbes can lead to the pathogenesis of AD. Among different types of microbes, human immunodeficiency virus-1 (HIV-1), herpes simplex virus-1 (HSV-1), Chlamydia pneumonia, Spirochetes and Candida albicans are frequently detected in the brain of AD patients. Amyloid-beta protein has demonstrated to exhibit antimicrobial properties upon encountering these pathogens. It can bind to microglial cells and astrocytes to activate immune response and neuroinflammation. Nevertheless, HIV-1 and HSV-1 can develop into latency whereas Chlamydia pneumonia, Spirochetes and Candida albicans can cause chronic infections. At this stage, the DNA of microbes remains undetectable yet active. This can act as the prolonged pathogenic stimulus that over-triggers the expression of Aβ-related genes, which subsequently lead to overproduction and deposition of Aβ plaque. This review will highlight the pathogenesis of each of the stated microbial infection, their association in AD pathogenesis as well as the effect of chronic infection in AD progression. Potential therapies for AD by modulating the microbiome have also been suggested. This review will aid in understanding the infectious manifestations of AD.
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Amyloid beta accumulation and consecutive deposition are unrelated to neuronal loss or cognitive decline.
“Although the amyloid cascade hypothesis has a wealth of evidence, it has repeatedly been demonstrated that Aβ accumulation and consecutive deposition are unrelated to neuronal loss or cognitive decline.”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [34]
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Flagged first, then by citations
Cited by
Sorted by citations
Nagori, K., Nakhate, K. T., Yadav, K., Ajazuddin, & Pradhan, M. (2023) · Future Pharmacology · doi:10.3390/futurepharmacol3040053 · Cited by 61 · see citing works
- Authors
- Phuna, Z. X., & Madhavan, P.
- Affiliations
- Taylor's University (MY)
- Corresponding author
- Madhavan, Priya
- Venue
- International Journal of Neuroscience
- Publisher
- Informa UK Limited
- Published
- 2022-03-14
- Volume
- 133
- Issue
- 10
- Pages
- 1071-1089
- ISSN
- 0020-7454 (ISSN-L)
- 1543-5245
- OpenAlex
- W4221056441
- Cited by
- 12
- References
- 187
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 2
- FWCI
- 0.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Taylor’s University Flagship Research Grant (TUFR/2017/002/04)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid hypothesis, chronic infection, infection hypothesis, amyloid-beta, HIV-1, herpes simplex virus type 1, Chlamydia pneumoniae, spirochetes, Candida albicans, neuroinflammation, microglia, astrocytes, microbial DNA, microbiome, Alzheimer's disease pathogenesis, Alzheimer's disease treatment
- MeSH terms
- Persistent Infection, Aged, Alzheimer Disease, Amyloid, Humans, Pneumonia, Amyloid beta-Peptides, Herpesvirus 1, Human
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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