ArticleTranslational psychiatry2021
APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline.
Article in Translational psychiatry, 2021. 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 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Beneficial Effect of Societal Factors on APOE-ε2 and ε4 Carriers' Brain Health: A Systematic Review.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Pooled it
- Depression and hippocampal subfield volume in older adults.Translational psychiatry · 2026Article
- APOE4 exacerbates glucocorticoid stress hormone-induced tau pathology via mitochondrial dysfunction.Cell death & disease · 2026Article
- Ventral hippocampal-postcentral gyrus functional connectivity mediates the association of APOE ε4 gene dose, depressive symptoms, and cognitive function in mild cognitive impairment with subsyndromal depression.Frontiers in aging neuroscience · 2026Article
- APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice.Neurobiology of disease · 2026Article
- Depression in older adults with epilepsy: Pathophysiology and management considerations.Epilepsy & behavior : E&B · 2025Review
- Defining the contributions of tau pathology in the amygdala to increasing depressive symptoms in aging.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Fueling the brain - the role of apolipoprotein E in brain energy metabolism and its implications for Alzheimer's disease.Translational psychiatry · 2025Review
- A Transcriptomic Signature of Depressive Symptoms in Late Life.Biological psychiatry global open science · 2025Article
- Sex differences in cognition, anxiety-phenotype and therapeutic effect of metformin in the aged apoE-TR mice.Biology of sex differences · 2025Article
- Identification of blood transcriptome modules associated with suicidal ideation in patients with major depressive disorder.Scientific reports · 2025Article
- APOE genotype-dependent differences in human astrocytic energy metabolism.Frontiers in cellular neuroscience · 2025Article
- Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain.PLoS computational biology · 2024Article
- Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain.bioRxiv : the preprint server for biology · 2024Article
- Article
- Cross-species analysis uncovers the mitochondrial stress response in the hippocampus as a shared mechanism in mouse early life stress and human depression.Neurobiology of stress · 2024Article
- ApoE4 dysregulation incites depressive symptoms and mitochondrial impairments in mice.Journal of cellular and molecular medicine · 2024Article
- Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer's Disease.International journal of molecular sciences · 2024Review
- The neurobiological mechanisms and therapeutic prospect of extracellular ATP in depression.CNS neuroscience & therapeutics · 2024Review
- Cell type-specific roles of APOE4 in Alzheimer disease.Nature reviews. Neuroscience · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Population-based studies reveal that apolipoprotein E (APOE) ε4 gene allele is closely associated with late-life depression (LLD). However, its exact role and underlying mechanism remain obscure. The current study found that aged apoE4-targeted replacement (TR) mice displayed obvious depression-like behavior when compared with age-matched apoE3-TR mice. Furthermore, apoE4 increased stress-induced depression-like behaviors, accompanied by declines in the hippocampal 5-HT (1A) radioligand [18F] MPPF uptake evidenced by positron emission tomography (PET). In [18F]-fluorodeoxyglucose PET ([18F]-FDG PET) analyses, the FDG uptake in the prefrontal cortex, temporal cortex and hippocampus of apoE4-TR mice significantly declined when compared with that of apoE3-TR mice after acute stress. Further biochemical analysis revealed that ATP levels in the prefrontal cortex of apoE4-TR mice decreased during aging or stress process and ATP supplementation effectively rescued the depression-like behaviors of elderly apoE4-TR mice. In primary cultured astrocytes from the cortex of apoE-TR mice, apoE4, when compared with apoE3, obviously decreased the mitochondrial membrane potential, mitochondrial respiration, and glycolysis in a culture time-dependent manner. Our findings highlight that apoE4 is a potential risk factor of depression in elderly population by impairing the glucose metabolism, reducing ATP level, and damaging mitochondrial functions in astrocytes, which indicates that in clinical settings ATP supplementation may be effective for elderly depression patients with apoE4 carrier.
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