<i>APOE</i> and immunity: Research highlights

Kloske, Courtney M; Barnum, Christopher J.; Batista, Andre Felipe; Bradshaw, Elizabeth M.; Brickman, Adam M.; Bu, Guojun; Dennison, Jessica; Gearon, Mary D; Goate, Alison; Haass, Christian; Heneka, Michael T.; Hu, William T.; Huggins, Lenique K.L.; Jones, Nahdia S; Koldamova, Radosveta; Lemere, Cynthia A.; Liddelow, Shane A.; Marcora, Edoardo; Marsh, Samuel E.; Nielsen, Henrietta M.; Petersen, Kellen K.; Petersen, Melissa; Piña‐Escudero, Stefanie Danielle; Qiu, Wei Qiao; Quiroz, Yakeel T.; Reiman, Eric M.; Sexton, Claire E.; Tansey, Malú G.; Tcw, Julia; Teunissen, Charlotte E.; Tijms, Betty M.; Kant, Rik van der; Wallings, Rebecca; Weninger, Stacie; Wharton, Whitney; Wilcock, Donna M.; Wishard, Tyler J.; Worley, Susan; Zetterberg, Henrik; Carrillo, María C.

doi:10.1002/alz.13020

Cited by 9 publications

(6 citation statements)

References 165 publications

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“…During the recovery phase, RNA levels of all upregulated APOE locus genes gradually returned to their untreated state, except for APOE. Its RNA level continued to rise even after the oxidative stress was removed, reinforcing the idea that APOE protein plays a crucial role in providing lipids that alleviate stress-induced damage as well as influencing mitochondrial biogenesis/dynamics and immunity [53,54]. Notably, we found that the RNA level of APOE increased the most in HMC3 cells, and the increase persisted during the recovery phase.…”

Section: Discussionsupporting

confidence: 84%

Mitochondrial Function-Associated APOE Locus and its Implication in Alzheimer’s Disease and Aging

Lee¹,

Leong²,

Chen³

et al. 2023

Preprint

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The APOE locus has garnered significant clinical interest because of its association with Alzheimer's disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions share a commonality of aging-related changes in mitochondrial function. This commonality is likely due to accumulative biological effects, partly exerted by the APOE locus. In this study, we investigated changes in mitochondrial structure/function-related markers using oxidative stress-induced human cellular models and postmortem brains (PMBs) from individuals with AD and normal controls. Our results reveal a range of expressional alterations, either up- or down-regulated, in these genes in response to oxidative stress. In contrast, we consistently observed an upregulation of multiple APOE locus genes in all cellular models and AD PMBs. Additionally, the effects of AD status on mitochondrial DNA copy number (mtDNA CN) varied depending on APOE genotype. Our findings imply a potential coregulation of APOE locus genes, possibly occurring within the same topologically associating domain (TAD) of the 3D chromosome conformation. The coordinated expression of APOE locus genes could impact mitochondrial function, contributing to the development of AD or longevity. Our study underscores the significant role of the APOE locus in modulating mitochondrial function and provides valuable insights into the underlying mechanisms of AD and aging, emphasizing the importance of this locus in clinical research.

show abstract

Section: Discussionsupporting

confidence: 84%

Mitochondrial Function-Associated APOE Locus and its Implication in Alzheimer’s Disease and Aging

Lee¹,

Leong²,

Chen³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…During the recovery phase, the RNA levels of all upregulated APOE locus genes gradually returned to their untreated state except for APOE . Its RNA level continued to rise even after the oxidative stress was removed, reinforcing the idea that the APOE protein plays a crucial role in providing lipids that alleviate stress-induced damage as well as influencing mitochondrial biogenesis/dynamics and immunity [ 59 , 60 ]. Notably, we found that the RNA level of APOE increased the most in HMC3 cells, and the increase persisted during the recovery phase.…”

Section: Discussionmentioning

confidence: 84%

APOE Locus-Associated Mitochondrial Function and Its Implication in Alzheimer’s Disease and Aging

Lee

Leong

Chen

et al. 2023

IJMS

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The Apolipoprotein E (APOE) locus has garnered significant clinical interest because of its association with Alzheimer’s disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions share a commonality of aging-related changes in mitochondrial function. This commonality is likely due to accumulative biological effects partly exerted by the APOE locus. In this study, we investigated changes in mitochondrial structure/function-related markers using oxidative stress-induced human cellular models and postmortem brains (PMBs) from individuals with AD and normal controls. Our results reveal a range of expressional alterations, either upregulated or downregulated, in these genes in response to oxidative stress. In contrast, we consistently observed an upregulation of multiple APOE locus genes in all cellular models and AD PMBs. Additionally, the effects of AD status on mitochondrial DNA copy number (mtDNA CN) varied depending on APOE genotype. Our findings imply a potential coregulation of APOE locus genes possibly occurring within the same topologically associating domain (TAD) of the 3D chromosome conformation. The coordinated expression of APOE locus genes could impact mitochondrial function, contributing to the development of AD or longevity. Our study underscores the significant role of the APOE locus in modulating mitochondrial function and provides valuable insights into the underlying mechanisms of AD and aging, emphasizing the importance of this locus in clinical research.

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“…Mutations in the APOE gene, which is responsible for the production of the apolipoprotein E protein -APOE, are one of the factors that increase the risk of Alzheimer's disease and cardiovascular disorders [6]. The APOE gene is located on the long arm of chromosome 19 q13.2 [7].…”

Section: Literature Review Resultsmentioning

confidence: 99%

Apoe as a Risk Factor for Alzheimer's Disease and Lipid Metabolism Disorders: Molecular Analysis

Kowalska,

Madej,

Szafraniec

et al. 2024

hpc

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The gene encoding apolipoprotein E (APOE) plays a key role in many biological processes, including lipid metabolism, brain homeostasis, and functioning of the circulatory system. APOE gene polymorphism is one of the most important risk factors in the context of Alzheimer's disease (AD), which is the most common cause of dementia. Different variants of APOE alleles, particularly APOE ε4, are associated with an increased risk of AD and accelerated progression of this disease. Mechanisms by which APOE ε4 contributes to AD pathogenesis include amyloid metabolism disorders, tautopenias, immune system dysfunction, and functional abnormalities of the blood-brain barrier. The APOE gene may play an important role not only in the pathogenesis of AD, but also in the development of cardiovascular diseases, such as coronary heart disease, stroke and atherosclerosis. As in AD, different variants of APOE alleles may affect lipid metabolism, inflammation, vascular functions and the processes of apoptosis, which translates into an increased risk of diseases. The article presents the current state of knowledge about the role and importance of the APOE gene in the pathomechanism of AD and cardiovascular diseases. Understanding molecular mechanisms and gene-environment interactions associated with APOE may contribute to changes in the diagnostic process. The development and improvement of genetic tests may help in early detection and treatment of diseases, and even, in some cases, prevent their occurrence.

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APOE and immunity: Research highlights

Cited by 9 publications

References 165 publications

Mitochondrial Function-Associated APOE Locus and its Implication in Alzheimer’s Disease and Aging

Mitochondrial Function-Associated APOE Locus and its Implication in Alzheimer’s Disease and Aging

APOE Locus-Associated Mitochondrial Function and Its Implication in Alzheimer’s Disease and Aging

Apoe as a Risk Factor for Alzheimer's Disease and Lipid Metabolism Disorders: Molecular Analysis

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