Genetic analysis of Vietnamese patients with early-onset Alzheimer's disease

Abstract

Purpose of the study: Alzheimer's disease (AD) is the most common type of dementia and its prevalence is rapidly increasing worldwide. Early-onset Alzheimer's disease (EOAD) constitutes of patients with age of onset earlier than 65 year-old and is known to be associated with genetic mutations. In this study, we reported the first genetic analysis of Vietnamese patients with EOAD.

Materials and methods: We analyzed targeted sequencing data obtained from a cohort of 51 Vietnamese EOAD patients to identify pathogenic variants in twenty nine well-characterized neurodengerative genes.

Results: We identified four missense mutations in APP/PSEN1 genes from six individuals, which accounts for 11.8% of all tested cases. Three of these mutations were previously reported as pathogenic and one mutation in the APP gene was newly identified and might be specific for Vietnamese patients. Our study also found eight individuals carrying homozygous APOE ε4 allele, the main risk factor gene for late-onset AD.

Conclusions: Our findings showed that mutation rate in APP/PSEN genes in Vietnamese EOAD patients is consistent with that in other ethnic groups. Although further functional studies are required to validate the pathogenesis of the new mutations, our study demonstrated the necessity of genetic screening for EOAD patients as well as additional genetic data collection in Vietnamese population.

Keywords:

• Alzheimer's disease (AD)
• early-onset Alzheimer's disease (EOAD)
• targeted sequencing

Acknowledgements

The authors thank Nhi Anh Vu, MD for critical comments on the study.

Authors contributions

TMT, QTTN, TCT recruited patients and performed clinical assessment of Alzheimer's disease.

TTHD, TTTD, HNN performed experiments.

LPD, DTN performed sequencing analysis.

HG, MDP and KDT designed experiments, analyzed the data and wrote the manuscript.

Availability of data and materials

The variant call set and the sequencing data are available upon reasonable request to the corresponding authors, subject to our policy of data privacy.

Consent for publication

All authors have read and approved the manuscript for publication.

Disclosure statement

The authors declare no conflict of interest.

Ethics approval and consent to participate

The institutional ethics committee of the University Medical Center, Ho Chi Minh City, Vietnam approved this study. All human genetic data of the participants was processed following the standard guidelines set by the University Medical Center, Ho Chi Minh City, Vietnam. All the participants have approved and provided written consent to the anonymous re-use of their genomic data for this study.

Additional information

Funding

This research was supported by a Ho Chi Minh City Foundation for Science and Technology Development grant (HCM-FOSTED) awarded by Department of Science and Technology at Ho Chi Minh City (grant number 1122/QĐ-SKHCN). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.