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Abstract <p>While the incidence of Alzheimer’s disease (AD) is constantly rising, AD treatments show symptomatic relief with modest benefits. One of the reasons is the multifactorial nature of AD involving both genetic and environmental risk factors. APOE ε4 allele is still known as the strongest genetic risk factor for late-onset AD. On the other hand, as approaches targeting Aβ and tau aggregates have not shown great success, attentions have shifted to other possible causative factors including mitochondria. Mitochondria are one of the organelles where AD pathogenic proteins aggregate and impair its bioenergetics and dynamics. Mitochondrial dynamics involves fission and fusion, two processes which are involved in mitochondrial life cycle and any disturbance in their balance can change normal mitochondrial function and distribution. Given the major role of <i>APOE</i> gene and mitochondrial dynamics in the etiology of AD, this study was aimed to investigate the effect of ε3 and ε4 isoforms of human <i>APOE</i> gene on mitochondrial dynamics and the changes in the expression levels of <i>Drp1</i> and <i>Marf</i> fission/fusion genes in <i>Drosophila</i> model of AD. For this purpose, total RNA was extracted from the brains of transgenic flies. Following cDNA synthesis, qRT-PCR was used to assess the expression level of mitochondrial dynamics genes. Our results showed decreased <i>Marf</i> expression level and increased <i>Drp1</i> expression level in Apoɛ4 and Apoɛ3 groups than control group. Such increase in <i>Drp1</i> expression level may indicate the activation of mitophagy to maintain mitochondrial homeostasis following mitochondrial dysfunction. Further studies are required to elucidate the underlying mechanism.</p>

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Investigating the Effect of Human APOE Gene on Mitochondrial Dynamics of Nervous System Cells in Drosophila Models of Alzheimer’s Disease

  • 期刊论文

  • 发表日期：

    2025年8月29日

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  • Asma Mirkamali,
  • Samaneh Reiszadeh Jahromi

摘要

Abstract

While the incidence of Alzheimer’s disease (AD) is constantly rising, AD treatments show symptomatic relief with modest benefits. One of the reasons is the multifactorial nature of AD involving both genetic and environmental risk factors. APOE ε4 allele is still known as the strongest genetic risk factor for late-onset AD. On the other hand, as approaches targeting Aβ and tau aggregates have not shown great success, attentions have shifted to other possible causative factors including mitochondria. Mitochondria are one of the organelles where AD pathogenic proteins aggregate and impair its bioenergetics and dynamics. Mitochondrial dynamics involves fission and fusion, two processes which are involved in mitochondrial life cycle and any disturbance in their balance can change normal mitochondrial function and distribution. Given the major role of APOE gene and mitochondrial dynamics in the etiology of AD, this study was aimed to investigate the effect of ε3 and ε4 isoforms of human APOE gene on mitochondrial dynamics and the changes in the expression levels of Drp1 and Marf fission/fusion genes in Drosophila model of AD. For this purpose, total RNA was extracted from the brains of transgenic flies. Following cDNA synthesis, qRT-PCR was used to assess the expression level of mitochondrial dynamics genes. Our results showed decreased Marf expression level and increased Drp1 expression level in Apoɛ4 and Apoɛ3 groups than control group. Such increase in Drp1 expression level may indicate the activation of mitophagy to maintain mitochondrial homeostasis following mitochondrial dysfunction. Further studies are required to elucidate the underlying mechanism.