ArticleMolecular neurodegeneration2017
Gene-environment interaction between lead and Apolipoprotein E4 causes cognitive behavior deficits in mice.
Article in Molecular neurodegeneration, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Systemic review of genetic and epigenetic factors underlying differential toxicity to environmental lead (Pb) exposure.Environmental science and pollution research international · 2022Pooled it
- Sex andToxics · 2026Article
- Cadmium-induced gut dysbiosis precedes the onset of hippocampus-dependent learning and memory deficits in mice.Toxicology · 2025Article
- Article
- Strain and sex effects on blood accumulation of lead, chromium, and cadmium in strains from the Collaborative Cross mouse population.bioRxiv : the preprint server for biology · 2025Article
- Unmasking Lead Exposure and Neurotoxicity: Epigenetics, Extracellular Vesicles, and the Gut-Brain Connection.Indian journal of clinical biochemistry : IJCB · 2025Article
- Urinary Metal Levels, Cognitive Test Performance, and Dementia in the Multi-Ethnic Study of Atherosclerosis.JAMA network open · 2024Article
- Synthesis, characterization and biological evaluation of aurones as potential neuroprotective agents.Future medicinal chemistry · 2024Article
- Cadmium inhibits calcium activity in hippocampal CA1 neurons of freely moving mice.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Article
- Inducible and Conditional Activation of Adult Neurogenesis Rescues Cadmium-Induced Hippocampus-Dependent Memory Deficits in ApoE4-KI Mice.International journal of molecular sciences · 2023Article
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- Gene-environment interactions in Alzheimer disease: the emerging role of epigenetics.Nature reviews. Neurology · 2022Review
- Effect of Chronic Cadmium Exposure on Brain and Liver Transporters and Drug-Metabolizing Enzymes in Male and Female Mice Genetically Predisposed to Alzheimer's Disease.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Adolescent cadmium exposure impairs cognition and hippocampal neurogenesis in C57BL/6 mice.Environmental toxicology · 2022Article
- Heavy metals and adult neurogenesis.Current opinion in toxicology · 2021Article
- Human Hair as a Possible Surrogate Marker of Retained Tissue Gadolinium: A Pilot Autopsy Study Correlating Gadolinium Concentrations in Hair With Brain and Other Tissues Among Decedents Who Received Gadolinium-Based Contrast Agents.Investigative radiology · 2020Article
- Iron-responsive-like elements and neurodegenerative ferroptosis.Learning & memory (Cold Spring Harbor, N.Y.) · 2020Review
- Inducible and Conditional Stimulation of Adult Hippocampal Neurogenesis Rescues Cadmium-Induced Impairments of Adult Hippocampal Neurogenesis and Hippocampus-Dependent Memory in Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Long-term probiotic intervention mitigates memory dysfunction through a novel H3K27me3-based mechanism in lead-exposed rats.Translational psychiatry · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAlzheimer's disease (AD) is characterized by progressive cognitive decline and memory loss. Environmental factors and gene-environment interactions (GXE) may increase AD risk, accelerate cognitive decline, and impair learning and memory. However, there is currently little direct evidence supporting this hypothesis.
methodsIn this study, we assessed for a GXE between lead and ApoE4 on cognitive behavior using transgenic knock-in (KI) mice that express the human Apolipoprotein E4 allele (ApoE4-KI) or Apolipoprotein E3 allele (ApoE3-KI). We exposed 8-week-old male and female ApoE3-KI and ApoE4-KI mice to 0.2% lead acetate via drinking water for 12 weeks and assessed for cognitive behavior deficits during and after the lead exposure. In addition, we exposed a second (cellular) cohort of animals to lead and assessed for changes in adult hippocampal neurogenesis as a potential underlying mechanism for lead-induced learning and memory deficits.
resultsIn the behavior cohort, we found that lead reduced contextual fear memory in all animals; however, this decrease was greatest and statistically significant only in lead-treated ApoE4-KI females. Similarly, only lead-treated ApoE4-KI females exhibited a significant decrease in spontaneous alternation in the T-maze. Furthermore, all lead-treated animals developed persistent spatial working memory deficits in the novel object location test, and this deficit manifested earlier in ApoE4-KI mice, with female ApoE4-KI mice exhibiting the earliest deficit onset. In the cellular cohort, we observed that the maturation, differentiation, and dendritic development of adult-born neurons in the hippocampus was selectively impaired in lead-treated female ApoE4-KI mice.
conclusionsThese data suggest that GXE between ApoE4 and lead exposure may contribute to cognitive impairment and that impaired adult hippocampal neurogenesis may contribute to these deficits in cognitive behavior. Together, these data suggest a role for GXE and sex differences in AD risk.
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