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Review
. 2022 Aug 19;17(1):53.
doi: 10.1186/s13024-022-00559-3.

When the infectious environment meets the AD brain

Tal Ganz  1   2 , Nina Fainstein  1   2 , Tamir Ben-Hur  3   4
Affiliations
Review

When the infectious environment meets the AD brain

Tal Ganz et al. Mol Neurodegener. .

Abstract

Background: The Amyloid theory of Alzheimer's disease (AD) suggests that the deposition of Amyloid β (Aβ) in the brain triggers a chain of events, involving the deposition of phosphorylated Tau and other misfolded proteins, leading to neurodegeneration via neuroinflammation, oxidative stress, and neurovascular factors. The infectious theory linked various infectious agents with the development of AD, raising the possibility that they serve as etiological causes of the disease. Are these theories mutually exclusive, or do they coincide?

Main body: In this review, we will discuss how the two theories converge. We present a model by which (1) the systemic infectious burden accelerates the development of AD brain pathology via bacterial Amyloids and other pathogen-associated molecular patterns (PAMPs), and (2) the developing AD brain pathology increases its susceptibility to the neurotoxicity of infectious agents -derived PAMPs, which drive neurodegeneration via activated microglia.

Conclusions: The reciprocal effects of amyloid deposition and systemic infectious burden may lead to a vicious cycle fueling Alzheimer's disease pathogenesis.

Keywords: Alzheimer’s disease; Amyloid-β; Infection; Lipopolysaccharides; Microglia; Neurodegeneration; Neuroinflammation; Pathogen associated molecular patterns.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Convergence of the amyloid and infectious theories of Alzheimer's Disease. We suggest that deposition of amyloid β causes increased visibility and susceptibility of the CNS to systemic infectious agents and their components coming from the systemic environment. In turn, infectious agents and PAMPs increase AD pathology and cortical neuron death. These result in a vicious cycle that accelerates neurodegeneration
See this image and copyright information in PMC

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