Alcohol and Alzheimer's Disease—Does Alcohol Dependence Contribute to Beta-Amyloid Deposition, Neuroinflammation and Neurodegeneration in Alzheimer's Disease?

Venkataraman, Ashwin; Kalk, Nicola J.; Sewell, Gavin W.; Ritchie, Craig W.; Lingford‐Hughes, Anne

doi:10.1093/alcalc/agw092

Cited by 59 publications

(49 citation statements)

References 71 publications

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“…Here, we show that chronic, intermittent exposure to alcohol‐vapor that results in motivational and somatic signs of withdrawal, produces glial activation in hippocampus and thalamus identified by in vitro slice autoradiography with the TSPO ligands [ 3 H]PK11195 and [ 3 H]PBR28. Similar patterns of drinking in humans have been associated with signs of neurotoxicity and cognitive impairment (Gupta & Warner, ; Kopera et al., ; Venkataraman, Kalk, Sewell, Ritchie, & Lingford‐Hughes, ), and microglial activation and neuroinflammation are plausible contributing factors. Our findings contribute to a growing literature that support the hypothesis that alcohol exposure is associated with neuroinflammation in the brain (Crews et al., ; Marshall, Geil, et al., ; Obernier et al., ).…”

Section: Discussionmentioning

confidence: 75%

Detecting neuroinflammation in the brain following chronic alcohol exposure in rats: A comparison between in vivo and in vitro TSPO radioligand binding

Tyler

Kim

Guo

et al. 2019

Eur J of Neuroscience

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Excessive alcohol consumption is associated with neuroinflammation, which likely contributes to alcohol‐related pathology. However, positron emission tomography (PET) studies using radioligands for the 18‐kDa translocator protein (TSPO), which is considered a biomarker of neuroinflammation, reported decreased binding in alcohol use disorder (AUD) participants compared to controls. In contrast, autoradiographic findings in alcohol exposed rats reported increases in TSPO radioligand binding. To assess if these discrepancies reflected differences between in vitro and in vivo methodologies, we compared in vitro autoradiography (using [3H]PBR28 and [3H]PK11195) with in vivo PET (using [11C]PBR28) in male, Wistar rats exposed to chronic alcohol‐vapor (dependent n = 10) and in rats exposed to air‐vapor (nondependent n = 10). PET scans were obtained with [11C]PBR28, after which rats were euthanized and the brains were harvested for autoradiography with [3H]PBR28 and [3H]PK11195 (n = 7 dependent and n = 7 nondependent), and binding quantified in hippocampus, thalamus, and parietal cortex. Autoradiography revealed significantly higher binding in alcohol‐dependent rats for both radioligands in thalamus and hippocampus (trend level for [3H]PBR28) compared to nondependent rats, and these group differences were stronger for [3H]PK11195 than [3H]PBR28. In contrast, PET measures obtained in the same rats showed no group difference in [11C]PBR28 binding. Our in vitro data are consistent with neuroinflammation associated with chronic alcohol exposure. Failure to observe similar increases in [11C]PBR28 binding in vivo suggests the possibility that a mechanism mediated by chronic alcohol exposure interferes with [11C]PBR28 binding to TSPO in vivo. These data question the sensitivity of PBR28 PET as a methodology to assess neuroinflammation in AUD.

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Section: Discussionmentioning

confidence: 75%

Detecting neuroinflammation in the brain following chronic alcohol exposure in rats: A comparison between in vivo and in vitro TSPO radioligand binding

Tyler

Kim

Guo

et al. 2019

Eur J of Neuroscience

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“…Alcohol has been examined as a risk factor of dementia, and a relationship between alcohol consumption and dementia has been evidenced. Although chronic alcohol abuse results in significant activation of neurodegenerative processes [23] and the prevalence of alcohol-related dementia represents about 10% of all cases of dementia [24], whether light-to-moderate drinking has any health benefits remains to be determined [25]. The relationship between the amount of alcohol intake and cognitive outcomes is complicated by differing definitions of high levels of alcohol consumption, by the duration of abuse, the age at which alcohol consumption begins, sex, and alternation of binge and withdrawal periods.…”

Section: Introductionmentioning

confidence: 99%

Relationship of Wine Consumption with Alzheimer’s Disease

et al. 2020

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Background: Alzheimer’s disease (AD), the most threatening neurodegenerative disease, is characterized by the loss of memory and language function, an unbalanced perception of space, and other cognitive and physical manifestations. The pathology of AD is characterized by neuronal loss and the extensive distribution of senile plaques and neurofibrillary tangles (NFTs). The role of environment and the diet in AD is being actively studied, and nutrition is one of the main factors playing a prominent role in the prevention of neurodegenerative diseases. In this context, the relationship between dementia and wine use/abuse has received increased research interest, with varying and often conflicting results. Scope and Approach: With this review, we aimed to critically summarize the main relevant studies to clarify the relationship between wine drinking and AD, as well as how frequency and/or amount of drinking may influence the effects. Key Findings and Conclusions: Overall, based on the interpretation of various studies, no definitive results highlight if light to moderate alcohol drinking is detrimental to cognition and dementia, or if alcohol intake could reduce risk of developing AD.

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“…Similarly, a prospective study of over 3000 subjects over 3 years found that light to moderate alcohol consumption reduced the risk of overall dementia by about 30% [ 83 ]. In contrast, a recent review of the literature to determine if alcohol consumption is a risk factor for AD concluded that alcohol use causes cognitive impairment by contributing to the neurodegenerative processes [ 84 ]. A systematic review concluded that there is as yet no consensus on this issue and that despite several studies, alcohol should not be considered methods to reduce AD risk [ 85 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of alcohol-treated microglia reveals downregulation of beta amyloid phagocytosis

Kalinin

González‐Prieto

Scheiblich

et al. 2018

J Neuroinflammation

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BackgroundMicroglial activation contributes to the neuropathology associated with chronic alcohol exposure and withdrawal, including the expression of inflammatory and anti-inflammatory genes. In the current study, we examined the transcriptome of primary rat microglial cells following incubation with alcohol alone, or alcohol together with a robust inflammatory stimulus.MethodsPrimary microglia were prepared from mixed rat glial cultures. Cells were incubated with 75 mM ethanol alone or with proinflammatory cytokines (“TII”: IL1β, IFNγ, and TNFα). Isolated mRNA was used for RNAseq analysis and qPCR. Effects of alcohol on phagocytosis were determined by uptake of oligomeric amyloid beta.ResultsAlcohol induced nitrite production in control cells and increased nitrite production in cells co-treated with TII. RNAseq analysis of microglia exposed for 24 h to alcohol identified 312 differentially expressed mRNAs (“Alc-DEs”), with changes confirmed by qPCR analysis. Gene ontology analysis identified phagosome as one of the highest-ranking KEGG pathways including transcripts regulating phagocytosis. Alcohol also increased several complement-related mRNAs that have roles in phagocytosis, including C1qa, b, and c; C3; and C3aR1. RNAseq analysis identified over 3000 differentially expressed mRNAs in microglia following overnight incubation with TII; and comparison to the group of Alc-DEs revealed 87 mRNAs modulated by alcohol but not by TII, including C1qa, b, and c. Consistent with observed changes in phagocytosis-related mRNAs, the uptake of amyloid beta1–42, by primary microglia, was reduced by alcohol.ConclusionsOur results define alterations that occur to microglial gene expression following alcohol exposure and suggest that alcohol effects on phagocytosis could contribute to the development of Alzheimer’s disease.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1184-7) contains supplementary material, which is available to authorized users.

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Alcohol and Alzheimer's Disease—Does Alcohol Dependence Contribute to Beta-Amyloid Deposition, Neuroinflammation and Neurodegeneration in Alzheimer's Disease?

Cited by 59 publications

References 71 publications

Detecting neuroinflammation in the brain following chronic alcohol exposure in rats: A comparison between in vivo and in vitro TSPO radioligand binding

Detecting neuroinflammation in the brain following chronic alcohol exposure in rats: A comparison between in vivo and in vitro TSPO radioligand binding

Relationship of Wine Consumption with Alzheimer’s Disease

Transcriptome analysis of alcohol-treated microglia reveals downregulation of beta amyloid phagocytosis

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