Background: Presenilin 1 (PSEN1) was suggested as the most common causative gene of
early onset Alzheimer’s Disease (AD).
Methods: Patient who presented progressive memory decline in her 40s was enrolled in this study. A
broad battery of neuropsychological tests and neuroimaging was applied to make the diagnosis. Genetic
tests were performed in the patient to evaluate possible mutations using whole exome sequencing. The
pathogenic nature of missense mutation and its 3D protein structure prediction were performed by in
silico prediction programs.
Results: A pathogenic mutation in PSEN1 (NM_000021.3: c.1027T>C p.Ala285Val), which was found
in a Korean EOAD patient. Magnetic resonance imaging scan showed mild left temporal lobe atrophy.
Hypometabolism appeared through 18F-fludeoxyglucose Positron Emission Tomography (FDG-PET)
scanning in bilateral temporal and parietal lobe, and 18F-Florbetaben-PET (FBB-PET) showed increased
amyloid deposition in bilateral frontal, parietal, temporal lobe and hence presumed preclinical
AD. Protein modeling showed that the p.Ala285Val is located in the random coil region and could result
in extra stress in this region, resulting in the replacement of an alanine residue with a valine. This
prediction was confirmed previous in vitro studies that the p.Trp165Cys resulted in an elevated
Aβ42/Aβ40 ratio in both COS-1 and HEK293 cell lines compared that of wild-type control.
Conclusion: Together, the clinical characteristics and the effect of the mutation would facilitate our
understanding of PSEN1 in AD pathogenesis for the disease diagnosis and treatment. Future in vivo
study is needed to evaluate the role of PSEN1 p.Ala285Val mutation in AD progression.