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Peer-reviewedCC BYFrontiers in neurology

Should ApoE4 gene editing therapy be approached with caution when AD is accompanied by retinal neurodegenerative diseases?

  • Yi Wenhua1
  • Ma Wenjing2
  • Dai Yan1
  • Li Fei1
  • Chen Juan1
  • Tang Xia1
  • Guan Yu1
  • Li Xin1
  • Huang Yanlin1
  • Guo Ya1
  • Yu Xuelin1
  • Luo Jing1
5 more authors
  • Jiang Meimin1
  • Li Wenyi1
  • Kang Yilin1
  • Liu Hongke1
  • Li Yating1
  1. 1Chengdu Fifth People's Hospital , ,
  2. 2Hospital of Chengdu University of Traditional Chinese Medicine , ,
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Abstract

Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for Alzheimer’s disease (AD), and ApoE4-directed gene editing and gene therapy have emerged as promising therapeutic strategies for AD, although they remain investigational and are not yet an established mainstream treatment. Interestingly, however, ApoE4 is reported to be associated with a reduced risk of retinal degenerative diseases such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). Therefore, should ApoE4 gene editing therapy be approached with caution when AD occurs concurrently with glaucoma, AMD, or DR? In view of these and based on the existing literature, the present study detailed the distinct roles of ApoE4 in AD, glaucoma, AMD, and DR, with a purpose to offer valuable insights into subsequent ApoE4 gene editing therapies. We also summarise the ApoE-targeted therapeutic programmes currently in preclinical and early clinical development, delineate the remaining translational challenges, and discuss how patients with coexisting retinal neurodegenerative disease might be evaluated and monitored.

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Cite

BibTeXRIS
BibTeX
@article{wenhua2026should,
  title = {{Should ApoE4 gene editing therapy be approached with caution when AD is accompanied by retinal neurodegenerative diseases?}},
  author = {Yi Wenhua and Ma Wenjing and Dai Yan and Li Fei and Chen Juan and Tang Xia and Guan Yu and Li Xin and Huang Yanlin and Guo Ya and Yu Xuelin and Luo Jing and Jiang Meimin and Li Wenyi and Kang Yilin and Liu Hongke and Li Yating},
  journal = {Frontiers in neurology},
  year = {2026},
  month = oct,
  doi = {10.3389/fneur.2026.1934307},
  url = {https://europepmc.org/article/PMC/PMC13669856},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Should ApoE4 gene editing therapy be approached with caution when AD is accompanied by retinal neurodegenerative diseases?
AU  - Yi Wenhua
AU  - Ma Wenjing
AU  - Dai Yan
AU  - Li Fei
AU  - Chen Juan
AU  - Tang Xia
AU  - Guan Yu
AU  - Li Xin
AU  - Huang Yanlin
AU  - Guo Ya
AU  - Yu Xuelin
AU  - Luo Jing
AU  - Jiang Meimin
AU  - Li Wenyi
AU  - Kang Yilin
AU  - Liu Hongke
AU  - Li Yating
PY  - 2026
DA  - 2026/10/01
JO  - Frontiers in neurology
DO  - 10.3389/fneur.2026.1934307
UR  - https://europepmc.org/article/PMC/PMC13669856
AB  - Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for Alzheimer’s disease (AD), and ApoE4-directed gene editing and gene therapy have emerged as promising therapeutic strategies for AD, although they remain investigational and are not yet an established mainstream treatment. Interestingly, however, ApoE4 is reported to be associated with a reduced risk of retinal degenerative diseases such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). Therefore, should ApoE4 gene editing therapy be approached with caution when AD occurs concurrently with glaucoma, AMD, or DR? In view of these and based on the existing literature, the present study detailed the distinct roles of ApoE4 in AD, glaucoma, AMD, and DR, with a purpose to offer valuable insights into subsequent ApoE4 gene editing therapies. We also summarise the ApoE-targeted therapeutic programmes currently in preclinical and early clinical development, delineate the remaining translational challenges, and discuss how patients with coexisting retinal neurodegenerative disease might be evaluated and monitored.
SN  - 1664-2295
ER  -