Publication: Analysis of 50 neurodegenerative genes in clinically diagnosed early-onset Alzheimer’s disease
Issued Date
2019-03-02
Resource Type
ISSN
14220067
16616596
16616596
Other identifier(s)
2-s2.0-85063957213
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Molecular Sciences. Vol.20, No.6 (2019)
Suggested Citation
Vo Van Giau, Vorapun Senanarong, Eva Bagyinszky, Seong Soo A. An, Sangyun Kim Analysis of 50 neurodegenerative genes in clinically diagnosed early-onset Alzheimer’s disease. International Journal of Molecular Sciences. Vol.20, No.6 (2019). doi:10.3390/ijms20061514 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/50233
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Analysis of 50 neurodegenerative genes in clinically diagnosed early-onset Alzheimer’s disease
Other Contributor(s)
Abstract
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and prion diseases have a certain degree of clinical, pathological, and molecular overlapping. Previous studies revealed that many causative mutations in AD, PD, and FTD/ALS genes could be found in clinical familial and sporadic AD. To further elucidate the missing heritability in early-onset Alzheimer’s disease (EOAD), we genetically characterized a Thai EOAD cohort by Next-Generation Sequencing (NGS) with a high depth of coverage, capturing variants in 50 previously recognized AD and other related disorders’ genes. A novel mutation, APP p.V604M, and the known causative variant, PSEN1 p.E184G, were found in two of the familiar cases. Remarkably, among 61 missense variants were additionally discovered from 21 genes out of 50 genes, six potential mutations including MAPT P513A, LRRK2 p.R1628P, TREM2 p.L211P, and CSF1R (p.P54Q and pL536V) may be considered to be probably/possibly pathogenic and risk factors for other dementia leading to neuronal degeneration. All allele frequencies of the identified missense mutations were compared to 622 control individuals. Our study provides initial evidence that AD and other neurodegenerative diseases may represent shades of the same disease spectrum, and consideration should be given to offer exactly embracing genetic testing to patients diagnosed with EOAD. Our results need to be further confirmed with a larger cohort from this area.