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A pathogenic PSEN1 Trp165Cys mutation associated with early-onset Alzheimer’s disease

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Authors
Van Giau, Vo; Pyun, Jung-Min; Suh, Jeewon; Bagyinszky, Eva; An, Seong Soo A; Kim, Sang Yun
Issue Date
2019-08-07
Publisher
BioMed Central
Citation
BMC Neurology, 19(1):188
Keywords
PathogenicPSEN1Trp165CysMutationAlzheimer’s disease
Abstract
Background
Presenilin-1 (PSEN1) is one of the causative genes for early onset Alzheimer’s disease (EOAD). Recently, emerging studies reported several novel PSEN1 mutations among Asian. We describe a male with EOAD had a pathogenic PSEN1 mutation.

Case presentation
A 53-year-old male presented with memory decline, followed by difficulty in finding ways. Patient had positive family history, since his mother and one of his brother was also affected with dementia. Brain magnetic resonance imaging (MRI) scan showed mild degree of atrophy of bilateral hippocampus and parietal lobe. 18F-Florbetaben-PET (FBB-PET) revealed increased amyloid deposition in bilateral frontal, parietal, temporal lobe and precuneus. Whole exome analysis revealed a heterozygous, probably pathogenic PSEN1 (c.695G > T, p.W165C) mutation. Interestingly, Trp165Cys mutation is located in trans membrane (TM)-III region, which is conserved between PSEN1/PSEN2. In vitro studies revealed that PSEN1 Trp165Cys could result in disturbances in amyloid metabolism. This prediction was confirmed by structure predictions and previous in vitro studies that the p.Trp165Cys could result in decreased Aβ42/Aβ40 ratios.

Conclusion
We report a case of EOAD having a pathogenic PSEN1 (Trp165Cys) confirmed with in silico and in vitro predictions.
ISSN
1471-2377
Language
English
URI
http://hdl.handle.net/10371/162603
DOI
https://doi.org/10.1186/s12883-019-1419-y
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Neurology (신경과학교실)Journal Papers (저널논문_신경과학교실)
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