ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2014
The cis-regulatory effect of an Alzheimer's disease-associated poly-T locus on expression of TOMM40 and apolipoprotein E genes.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- TOMM40 genetic variants associated with healthy aging and longevity: a systematic review.BMC geriatrics · 2022Pooled it
- Genotypic Effects of the TOMM40'523 Variant and APOE on Longitudinal Cognitive Change over 4 Years: The TOMMORROW Study.The journal of prevention of Alzheimer's disease · 2023Trial
- Article
- Bioenergetics and lipid metabolism in Alzheimer's disease: From cell biology to systemic health.Journal of internal medicine · 2026Review
- SENP6 Maintains Mitochondrial Homeostasis by Regulating Mitochondrial Protein Import Through deSUMOylation of TOM40.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Genetics of Amyloid Deposition: A Systematic Review of Genome-Wide Association Studies Using Amyloid PET Imaging in Alzheimer's Disease.Journal of imaging · 2025Review
- Leveraging multiomic approaches to elucidate mechanisms of heterogeneity in Alzheimer's disease: Neuropsychiatric symptoms, co-pathologies, and sex differences.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Rare missense variants inJournal of medical genetics · 2025Article
- Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Integrative single-nucleus multi-omics analysis prioritizes candidate cis and trans regulatory networks and their target genes in Alzheimer's disease brains.Cell & bioscience · 2023Article
- Article
- Article
- TOMM40 '523 Genotype Distinguishes Patterns of Cognitive Improvement for Executive Function in APOEɛ3 Homozygotes.Journal of Alzheimer's disease : JAD · 2023Article
- The APOE-TOMM40 Humanized Mouse Model: Characterization of Age, Sex, and PolyT Variant Effects on Gene Expression.Journal of Alzheimer's disease : JAD · 2023Article
- Prevailing Antagonistic Risks in Pleiotropic Associations with Alzheimer's Disease and Diabetes.Journal of Alzheimer's disease : JAD · 2023Article
- An increase in mitochondrial TOM activates apoptosis to drive retinal neurodegeneration.Scientific reports · 2022Article
- APOE ɛ4 allele and TOMM40-APOC1 variants jointly contribute to survival to older ages.Aging cell · 2022Article
- Statistical testing in transcriptomic-neuroimaging studies: A how-to and evaluation of methods assessing spatial and gene specificity.Human brain mapping · 2022Article
- Definitive roles of TOMM40-APOE-APOC1 variants in the Alzheimer's risk.Neurobiology of aging · 2022Article
- In Alzheimer-prone brain regions, metabolism and risk-gene expression are strongly correlated.Brain communications · 2022Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundWe investigated the genomic region spanning the Translocase of the Outer Mitochondrial Membrane 40-kD (TOMM40) and Apolipoprotein E (APOE) genes, that has been associated with the risk and age of onset of late-onset Alzheimer's disease (LOAD) to determine whether a highly polymorphic, intronic poly-T within this region (rs10524523; hereafter, 523) affects expression of the APOE and TOMM40 genes. Alleles of this locus are classified as S, short; L, long; and VL, very long based on the number of T residues.
methodsWe evaluated differences in APOE messenger RNA (mRNA) and TOMM40 mRNA levels as a function of the 523 genotype in two brain regions from APOE ε3/ε3 white autopsy-confirmed LOAD cases and normal controls. We further investigated the effect of the 523 locus in its native genomic context using a luciferase expression system.
resultsThe expression of both genes was significantly increased with disease. Mean expression of APOE and TOMM40 mRNA levels were higher in VL homozygotes compared with S homozygotes in the temporal and occipital cortexes from normal and LOAD cases. Results of a luciferase reporter system were consistent with the human brain mRNA analysis; the 523 VL poly-T resulted in significantly higher expression than the S poly-T. Although the effect of poly-T length on reporter expression was the same in HepG2 hepatoma and SH-SY5Y neuroblastoma cells, the magnitude of the effect was greater in the neuroblastoma than in the hepatoma cells, which implies tissue-specific modulation of the 523 poly-T.
conclusionsThese results suggest that the 523 locus may contribute to LOAD susceptibility by modulating the expression of TOMM40 and/or APOE transcription.
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