Li J, Zhou FL, Chen JJ, Lin ZJ, Shi X, Zhang GG, Yang HJ, Dong MJ, Yi L, Hu J, Chen XH. Novel PSEN1 (Q223 L) mutation causes early-onset Alzheimer’s disease: A case report. World J Radiol 2026; 18(6): 116652 [DOI: 10.4329/wjr.116652]
Corresponding Author of This Article
Xu-Hui Chen, MD, PhD, Department of Neurology, Peking University Shenzhen Hospital, Lianhua Road, Shenzhen 518000, Guangdong Province, China. xuhuichen@pkuszh.com
Research Domain of This Article
Neurosciences
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case-report
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Li J, Zhou FL, Chen JJ, Lin ZJ, Shi X, Zhang GG, Yang HJ, Dong MJ, Yi L, Hu J, Chen XH. Novel PSEN1 (Q223 L) mutation causes early-onset Alzheimer’s disease: A case report. World J Radiol 2026; 18(6): 116652 [DOI: 10.4329/wjr.116652]
World J Radiol. Jun 28, 2026; 18(6): 116652 Published online Jun 28, 2026. doi: 10.4329/wjr.116652
Novel PSEN1 (Q223 L) mutation causes early-onset Alzheimer’s disease: A case report
Jie Li, Fen-Li Zhou, Juan-Juan Chen, Zhi-Jian Lin, Xin Shi, Guo-Gao Zhang, Hong-Jie Yang, Meng-Jie Dong, Li Yi, Jun Hu, Xu-Hui Chen
Jie Li, Fen-Li Zhou, Juan-Juan Chen, Zhi-Jian Lin, Xin Shi, Guo-Gao Zhang, Li Yi, Jun Hu, Xu-Hui Chen, Department of Neurology, Peking University Shenzhen Hospital, Shenzhen 518000, Guangdong Province, China
Jie Li, Jun Hu, Xu-Hui Chen, Shenzhen Key Laboratory for Neuronal Structural Biology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, Guangdong Province, China
Hong-Jie Yang, Meng-Jie Dong, Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen 518000, Guangdong Province, China
Co-corresponding authors: Jun Hu and Xu-Hui Chen.
Author contributions: Li J and Chen XH conceptualized and designed the case report, drafted and revised the initial manuscript; Zhou FL, Chen JJ, Lin ZJ, Shi X, and Zhang GG contributed to the supervision, and writing, review and editing of the manuscript; Yi L and Hu J contributed to the conception and design of the manuscript; Yang HJ and Dong MJ performed positron emission computed tomography analysis; Hu J and Chen XH contributed equally to this article, they are the co-corresponding authors of this manuscript; and all authors have reviewed the results and approved the final version of the manuscript.
Supported by Shenzhen Basic Research Program, No. JCYJ20241202124859016.
Informed consent statement: The informed consent form has been signed.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Corresponding author: Xu-Hui Chen, MD, PhD, Department of Neurology, Peking University Shenzhen Hospital, Lianhua Road, Shenzhen 518000, Guangdong Province, China. xuhuichen@pkuszh.com
Received: November 17, 2025 Revised: December 31, 2025 Accepted: May 6, 2026 Published online: June 28, 2026 Processing time: 220 Days and 12.4 Hours
Abstract
BACKGROUND
Mutations in the PSEN1, PSEN2, and APP genes are known to cause Alzheimer’s disease (AD). Among these, PSEN1 mutations are the most frequent causes of autosomal dominant early-onset AD (EOAD). Patients harboring pathogenic mutations often exhibit considerable clinical heterogeneity. Identifying novel mutations and analyzing their associations with clinical cases is crucial for advancing our understanding of the pathogenesis of AD.
CASE SUMMARY
This report describes the clinical presentation of a family with EOAD. The proband was a 43-year-old Chinese female who presented with a three-year history of cognitive decline for 3 years. Magnetic resonance imaging demonstrated diffuse cerebral cortical atrophy. Next-generation sequencing identified a novel heterozygous c.668A>T mutation in PSEN1, which resulted in a p.Gln223 Leu. cerebrospinal fluid biomarker analysis revealed abnormal levels of amyloid and tau, indicative of underlying Alzheimer’s pathology. Furthermore, 18F-flortaucipir (AV-1451) positron emission topography and 18F-florbetapir (AV-45) positron emission topography imaging demonstrated extensive cerebral amyloid beta and tau deposition.
CONCLUSION
We report a novel pathogenic PSEN1 mutation, Q223 L, identified for the first time in a Chinese family with EOAD.
Core Tip: We identified a novel p.Gln223 Leu mutation in PSEN1 in a 43-year-old Chinese female with autosomal dominant early-onset Alzheimer’s disease (EOAD). Comprehensive clinical, neuroimaging, cerebrospinal fluid biomarkers, and 18F-florbetapir/18F-flortaucipir positron emission topography findings confirmed typical Alzheimer’s pathology. This mutation occurs at a mutational hotspot of PSEN1, is predicted to be pathogenic by in silico analysis, and has not been previously reported in public databases. Our report expands the mutation spectrum of PSEN1, enriches genotype - phenotype correlations of familial EOAD, and provides new evidence for the genetic diagnosis, pathogenesis research, and genetic counseling of EOAD.
