BRIEF RESEARCH REPORT article
Front. Aging Neurosci.
Sec. Parkinson’s Disease and Aging-related Movement Disorders
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1632480
This article is part of the Research TopicBiomarkers for early detection and progression of Parkinson’s Disease: Integrating genomic, proteomic, imaging, and clinical advancesView all articles
Elucidating the role of APOE ε4 gene variants in the Clinical Manifestation of Parkinson’s Disease
Provisionally accepted
Gita Vita Soraya1*
Yusran Ady Fitrah1
Andi Kurnia Bintang1
Muhammad Akbar1
Alfi Raudatil Jannah2
Zulvikar Syambani Ulhaq3
Jumraini Tammasse1
Cahyono Kaelan1
Muhammad Nasrum Massi1Ai Obinata2
Norikazu Hara2Akinori Miyashita2*
Takeshi Ikeuchi2- 1Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
- 2Brain Research Institute, Niigata University, Niigata, Niigata, Japan
- 3National Research and Innovation Agency (BRIN), Bogor, Jakarta, Indonesia
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Introduction. Parkinson’s Disease (PD) is the most common movement disorder, and remains a major cause of mortality and morbidity worldwide. Studies have uncovered the potential role of the Apolipoprotein (APOE) gene in PD, although results have been conflicting. This study aimed to characterize the APOE ε4 status of Indonesian PD subjects and perform a meta-analysis to elucidate it's role in PD onset age, disease severity, and cognition. Methods. APOE ε4 genotyping was performed on PD patients and their respective healthy families. Clinical parameters were obtained from PD patients. Secondly, we conducted a meta-analysis on the role of APOE ε4, with studies collected until January 2025. Retrieved parameters include the number of PD APOE ε4 allele carriers and non-carriers, age of onset, disease severity, and mini-mental state examination (MMSE) scores. Results. Four of the 7 recruited subjects were APOE ε4 carriers, with 2 out of 3 PD subjects of APOE ε4 carrier status. In the meta-analysis, 14 included studies revealed a significantly younger age of onset in APOE ε4 carriers (SMD = – 0.16, 95%CI –0.24 to –0.08, p = 0.0001) relative to non-carriers. Six included studies revealed no significant difference in the Hoehn and Yahr disease severity, and 4 included studies showed no significant difference in MMSE scores of carriers versus non-carriers. Conclusion. The APOE ε4 allele is common in this preliminary study of 3 PD subjects. Our meta-analysis revealed a significantly earlier age-of-onset among APOE ε4 carriers relative to non-carriers, but no difference in disease severity and MMSE scores.
Keywords: Parkinson's disease, apolipoprotein gene, movement disorder, Onset age, severity
Received: 21 May 2025; Accepted: 30 Sep 2025.
Copyright: © 2025 Soraya, Fitrah, Bintang, Akbar, Jannah, Ulhaq, Tammasse, Kaelan, Massi, Obinata, Hara, Miyashita and Ikeuchi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Gita Vita Soraya, gitavitasoraya@unhas.ac.id
Akinori Miyashita, miyashi2020.bri@niigata-u.ac.jp
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