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Review
. 2022 Sep 9:15:910298.
doi: 10.3389/fnmol.2022.910298. eCollection 2022.

Innate immune activation: Parallels in alcohol use disorder and Alzheimer's disease

Adriana Ramos  1 , Radhika S Joshi  1 , Gyongyi Szabo  1   2
Affiliations
Review

Innate immune activation: Parallels in alcohol use disorder and Alzheimer's disease

Adriana Ramos et al. Front Mol Neurosci. .

Abstract

Alcohol use disorder is associated with systemic inflammation and organ dysfunction especially in the liver and the brain. For more than a decade, studies have highlighted alcohol abuse-mediated impairment of brain function and acceleration of neurodegeneration through inflammatory mechanisms that directly involve innate immune cells. Furthermore, recent studies indicate overlapping genetic risk factors between alcohol use and neurodegenerative disorders, specifically regarding the role of innate immunity in the pathomechanisms of both areas. Considering the pressing need for a better understanding of the relevance of alcohol abuse in dementia progression, here we summarize the molecular mechanisms of neuroinflammation observed in alcohol abuse and Alzheimer's disease, the most common cause of dementia. In addition, we highlight mechanisms that are already established in the field of Alzheimer's disease that may be relevant to explore in alcoholism to better understand alcohol mediated neurodegeneration and dementia, including the relevance of the liver-brain axis.

Keywords: Alzheimer’s disease; alcohol; innate immunity; liver-brain axis; microglia; neuroinflammation.

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Conflict of interest statement

GS was the editor-in-Chief of Hepatology Communication., consults for Cyta Therapeutics, Durect, Evive, Merck, Novartis, Pandion Therapeutics, Pfizer, Surrozen and Terra Firma, received royalties from UptoDate and Springer and also holds equity in Glympse Bio, Zomagen and Satellite Bio. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Microglia play critical role in alcohol-induced neuroinflammation. Alcohol abuse leads to microglia activation primarily through TLR4, 2, and NLRP3 inflammasomes. Consequently, microglia show increased proliferation, morphological transformation, release of cytokines, chemokines, EVs and immune mediators. This results in infiltration of peripheral macrophages, neurotoxicity, synapse loss and modulation of ethanol-induced behaviors.
FIGURE 2
FIGURE 2
Liver-brain axis in alcohol use disorder (AUD) and Alzheimer’s disease (AD). (A) Various modes of communication between the peripheral circulation and the brain. (B) AUD leads to innate immune activation in liver that results in secretion of cytokines, chemokines, toxic lipids, EVs, and hepatotoxins in the circulation that can reach the CNS. In AD, altered liver metabolism of lipids and bile acids can modulate Aβ levels in the periphery and consequently in the CNS.
See this image and copyright information in PMC

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