Amyloid, tau, pathogen infection and antimicrobial protection in Alzheimer's disease -conformist, nonconformist, and realistic prospects for AD pathogenesis

Hongmei Li, Chia-Chen Liu, Hui Zheng, Timothy Y. Huang

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Background: Alzheimer's disease (AD) is a fatal disease that threatens the quality of life of an aging population at a global scale. Various hypotheses on the etiology of AD have been developed over the years to guide efforts in search of therapeutic strategies. Main body: In this review, we focus on four AD hypotheses currently relevant to AD onset: the prevailing amyloid cascade hypothesis, the well-recognized tau hypothesis, the increasingly popular pathogen (viral infection) hypothesis, and the infection-related antimicrobial protection hypothesis. In briefly reviewing the main evidence supporting each hypothesis and discussing the questions that need to be addressed, we hope to gain a better understanding of the complicated multi-layered interactions in potential causal and/or risk factors in AD pathogenesis. As a defining feature of AD, the existence of amyloid deposits is likely fundamental to AD onset but is insufficient to wholly reproduce many complexities of the disorder. A similar belief is currently also applied to hyperphosphorylated tau aggregates within neurons, where tau has been postulated to drive neurodegeneration in the presence of pre-existing Aβ plaques in the brain. Although infection of the central nerve system by pathogens such as viruses may increase AD risk, it is yet to be determined whether this phenomenon is applicable to all cases of sporadic AD and whether it is a primary trigger for AD onset. Lastly, the antimicrobial protection hypothesis provides insight into a potential physiological role for Aβ peptides, but how Aβ/microbial interactions affect AD pathogenesis during aging awaits further validation. Nevertheless, this hypothesis cautions potential adverse effects in Aβ-targeting therapies by hindering potential roles for Aβ in anti-viral protection. Conclusion: AD is a multi-factor complex disorder, which likely requires a combinatorial therapeutic approach to successfully slow or reduce symptomatic memory decline. A better understanding of how various causal and/or risk factors affecting disease onset and progression will enhance the likelihood of conceiving effective treatment paradigms, which may involve personalized treatment strategies for individual patients at varying stages of disease progression.

Original languageEnglish (US)
Article number34
JournalTranslational Neurodegeneration
Volume7
Issue number1
DOIs
StatePublished - Dec 24 2018

Fingerprint

Amyloid
Alzheimer Disease
Infection
Disease Progression
Microbial Interactions
Therapeutics
Amyloid Plaques
Virus Diseases
Quality of Life
Viruses
Neurons

Keywords

  • Alzheimer's disease
  • Amyloid hypothesis
  • Amyloid-beta
  • Antimicrobial protection
  • Pathogen hypothesis
  • Tau hypothesis
  • Viral infection

ASJC Scopus subject areas

  • Clinical Neurology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Amyloid, tau, pathogen infection and antimicrobial protection in Alzheimer's disease -conformist, nonconformist, and realistic prospects for AD pathogenesis. / Li, Hongmei; Liu, Chia-Chen; Zheng, Hui; Huang, Timothy Y.

In: Translational Neurodegeneration, Vol. 7, No. 1, 34, 24.12.2018.

Research output: Contribution to journalReview article

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abstract = "Background: Alzheimer's disease (AD) is a fatal disease that threatens the quality of life of an aging population at a global scale. Various hypotheses on the etiology of AD have been developed over the years to guide efforts in search of therapeutic strategies. Main body: In this review, we focus on four AD hypotheses currently relevant to AD onset: the prevailing amyloid cascade hypothesis, the well-recognized tau hypothesis, the increasingly popular pathogen (viral infection) hypothesis, and the infection-related antimicrobial protection hypothesis. In briefly reviewing the main evidence supporting each hypothesis and discussing the questions that need to be addressed, we hope to gain a better understanding of the complicated multi-layered interactions in potential causal and/or risk factors in AD pathogenesis. As a defining feature of AD, the existence of amyloid deposits is likely fundamental to AD onset but is insufficient to wholly reproduce many complexities of the disorder. A similar belief is currently also applied to hyperphosphorylated tau aggregates within neurons, where tau has been postulated to drive neurodegeneration in the presence of pre-existing Aβ plaques in the brain. Although infection of the central nerve system by pathogens such as viruses may increase AD risk, it is yet to be determined whether this phenomenon is applicable to all cases of sporadic AD and whether it is a primary trigger for AD onset. Lastly, the antimicrobial protection hypothesis provides insight into a potential physiological role for Aβ peptides, but how Aβ/microbial interactions affect AD pathogenesis during aging awaits further validation. Nevertheless, this hypothesis cautions potential adverse effects in Aβ-targeting therapies by hindering potential roles for Aβ in anti-viral protection. Conclusion: AD is a multi-factor complex disorder, which likely requires a combinatorial therapeutic approach to successfully slow or reduce symptomatic memory decline. A better understanding of how various causal and/or risk factors affecting disease onset and progression will enhance the likelihood of conceiving effective treatment paradigms, which may involve personalized treatment strategies for individual patients at varying stages of disease progression.",
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