ArticleActa neuropathologica communications2019
Aldehyde dehydrogenase 2 activity and aldehydic load contribute to neuroinflammation and Alzheimer's disease related pathology.
Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Association Study and Meta-Analysis of Polymorphisms and Blood mRNA Expression of the ALDH2 Gene in Patients with Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2022Pooled it
- Estradiol Replacement Modulates Synaptic Transmission-Related Proteins in the Hippocampus of Ovariectomized Rats: An Exploratory Proteomic Approach.Journal of neurochemistry · 2026Article
- Mitochondrial vulnerability to aldehydic load and the role mitochondrial aldehyde dehydrogenases.Pharmacological research · 2026Review
- Common human ALDH1B1 and ALDH2 variants increase neuroinflammatory response to a single ethanol dose in mice.Science advances · 2026Article
- Integrated transcriptomic profiling combined withFrontiers in aging neuroscience · 2026Article
- Current Perspectives on Oxytocin and Alzheimer's Disease-Related Symptoms.Current Alzheimer research · 2026Review
- Beyond the Flush: Reframing ALDH2 Deficiency as a Public Health Risk.Public health genomics · 2026Article
- The Pathological Role and Therapeutic potential of ALDH2 in acrolein detoxification Following Spinal Cord Injury in Mice.bioRxiv : the preprint server for biology · 2025Article
- L-Theanine Mitigates Acute Alcoholic Intestinal Injury by Activating the HIF-1 Signaling Pathway to Regulate the TLR4/NF-κB/HIF-1α Axis in Mice.Nutrients · 2025Article
- Methylglyoxal Formation-Metabolic Routes and Consequences.Antioxidants (Basel, Switzerland) · 2025Review
- World no-tobacco: effects of second-hand smoke (SHS) and vapors on the developing and adult brain.Frontiers in pharmacology · 2025Review
- Supervised multiple kernel learning approaches for multi-omics data integration.BioData mining · 2024Article
- Mitochondrial Aldehyde Dehydrogenase 2 (ALDH2) Protects against Binge Alcohol-Mediated Gut and Brain Injury.Cells · 2024Article
- The aldehyde dehydrogenase 2 rs671 variant enhances amyloid β pathology.Nature communications · 2024Article
- Spatial amine metabolomics and histopathology reveal localized brain alterations in subacute traumatic brain injury and the underlying mechanism of herbal treatment.CNS neuroscience & therapeutics · 2024Article
- Morphological profiling in human neural progenitor cells classifies hits in a pilot drug screen for Alzheimer's disease.Brain communications · 2024Article
- A common East-Asian ALDH2 mutation causes metabolic disorders and the therapeutic effect of ALDH2 activators.Nature communications · 2023Article
- Alcohol as a Modifiable Risk Factor for Alzheimer's Disease-Evidence from Experimental Studies.International journal of molecular sciences · 2023Review
- New Insights into Alzheimer's Disease: Novel Pathogenesis, Drug Target and Delivery.Pharmaceutics · 2023Review
- SGLT2 inhibitor ameliorates endothelial dysfunction associated with the commonScience translational medicine · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Aldehyde dehydrogenase 2 deficiency (ALDH2*2) causes facial flushing in response to alcohol consumption in approximately 560 million East Asians. Recent meta-analysis demonstrated the potential link between ALDH2*2 mutation and Alzheimer's Disease (AD). Other studies have linked chronic alcohol consumption as a risk factor for AD. In the present study, we show that fibroblasts of an AD patient that also has an ALDH2*2 mutation or overexpression of ALDH2*2 in fibroblasts derived from AD patients harboring ApoE ε4 allele exhibited increased aldehydic load, oxidative stress, and increased mitochondrial dysfunction relative to healthy subjects and exposure to ethanol exacerbated these dysfunctions. In an in vivo model, daily exposure of WT mice to ethanol for 11 weeks resulted in mitochondrial dysfunction, oxidative stress and increased aldehyde levels in their brains and these pathologies were greater in ALDH2*2/*2 (homozygous) mice. Following chronic ethanol exposure, the levels of the AD-associated protein, amyloid-β, and neuroinflammation were higher in the brains of the ALDH2*2/*2 mice relative to WT. Cultured primary cortical neurons of ALDH2*2/*2 mice showed increased sensitivity to ethanol and there was a greater activation of their primary astrocytes relative to the responses of neurons or astrocytes from the WT mice. Importantly, an activator of ALDH2 and ALDH2*2, Alda-1, blunted the ethanol-induced increases in Aβ, and the neuroinflammation in vitro and in vivo. These data indicate that impairment in the metabolism of aldehydes, and specifically ethanol-derived acetaldehyde, is a contributor to AD associated pathology and highlights the likely risk of alcohol consumption in the general population and especially in East Asians that carry ALDH2*2 mutation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.