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BMC Neurology
Published in: BMC Neurology 1/2019

Open Access 01-12-2019 | Magnetic Resonance Imaging | Case report

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

Authors: Vo Van Giau, Jung-Min Pyun, Jeewon Suh, Eva Bagyinszky, Seong Soo A. An, Sang Yun Kim

Published in: BMC Neurology | Issue 1/2019

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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.
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Metadata
Title
A pathogenic PSEN1 Trp165Cys mutation associated with early-onset Alzheimer’s disease
Authors
Vo Van Giau
Jung-Min Pyun
Jeewon Suh
Eva Bagyinszky
Seong Soo A. An
Sang Yun Kim
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2019
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-019-1419-y

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