Aldehyde-Induced DNA and Protein Adducts as Biomarker Tools for Alcohol Use Disorder
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Alcohol use disorder (AUD) screening frequently involves questionnaires complemented by laboratory work to monitor alcohol use and/or evaluate AUD-associated complications. Here we suggest that measuring aldehyde-induced DNA and protein adducts produced during alcohol metabolism may lead to earlier detection of AUD and AUD-associated complications compared with existing biomarkers. Use of aldehyde-induced adducts to monitor AUD may also be important when considering that approximately 540 million people bear a genetic variant of aldehyde dehydrogenase 2 (ALDH2) predisposing this population to aldehyde-induced toxicity with alcohol use. We posit that measuring aldehyde-induced adducts may provide a means to improve precision medicine approaches, taking into account lifestyle choices and genetics to evaluate AUD and AUD-associated complications.
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AA-protein adducts are widely present in the brains of alcohol-exposed rodents or people with AUD; after alcohol consumption they are rapidly produced in the cerebral cortex primarily with mitochondrial proteins and localized in white matter, deep layers of the frontal cortex, and molecular layer of the cerebellum; they also form AA-tubulin adducts causing microtubule malformation and cytoskeletal
“AA-protein adducts are widely present in the brains of alcohol-exposed rodents or people with alcohol use disorder (AUD)189–192.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [192]
Acetaldehyde in the brain alters DNA integrity and neuronal viability; it can form AA-DNA adducts in the brain and peripheral blood leukocytes of people with AUD since ethanol, acetaldehyde, and lipid aldehydes such as MDA and 4-HNE can inhibit DNA repair enzymes; dual mechanisms of elevated AA-DNA adducts and suppressed DNA repair may contribute to genetic instability and DNA mutations, promoting
“The presence of acetaldehyde in the brain also alters DNA integrity and neuronal viability.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [192]
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Self-citationDevelopment of an Acetaldehyde-Specific Fluorescent Probe: Strategy and Applications
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- Authors
- Heymann, H. M., Gardner, A. M., & Gross, E. R.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Gross, Eric R.
- Venue
- Trends in Molecular Medicine
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 24
- Issue
- 2
- Pages
- 144-155
- ISSN
- 1471-4914 (ISSN-L)
- PMC
- PMC6483939
- OpenAlex
- W2785745834
- Cited by
- 60
- References
- 93
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 10 · 2023: 9 · 2022: 13 · 2021: 8 · 2020: 3 · 2019: 5 · 2018: 2
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Trends in Molecular Medicine (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (GM119522)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- alcoholism, aldehyde adducts, DNA adducts, protein adducts, biomarkers, alcohol metabolism, ALDH2, aldehyde toxicity, precision medicine
- MeSH terms
- Aldehyde Dehydrogenase, Mitochondrial, Alcoholism, Aldehydes, Humans, Mutation, Biomarkers, DNA Adducts
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