PSEN1 variants in Korean patients with clinically suspicious early-onset familial Alzheimer's disease

Sci Rep. 2020 Feb 26;10(1):3480. doi: 10.1038/s41598-020-59829-z.

Abstract

Pathogenic variants in the PSEN1 gene are known to be the most common cause of early-onset Alzheimer's disease but there are few data on the frequency and spectrum of PSEN1 variants in Korea. In this study, we investigated PSEN1 variants in a consecutive series of clinically suspicious early-onset familial AD (EOFAD) Korean patients and their clinical characteristics and imaging findings. From January 2007 to December 2013, EOFAD patients with very early onset AD (<50 yr), early onset AD (<60 yr) with two or more relatives with AD, and early onset AD (<60 yr) with one or more first-degree relatives with very early onset AD (<50 yr) were enrolled in this study. Sequence analysis of the PSEN1 gene was performed by Sanger sequencing. Neuroimaging data and conventional brain MRIs and FDG-PET and/or [11C] PiB-PET scans were analyzed in patients with PSEN1 variants. Among the 28 patients with EOFAD, six (21.4%, 6/28) patients had pathogenic or likely pathogenic variants in the PSEN1 gene. Two pathogenic variants were p.Glu120Lys and p.Ser170Phe and four likely pathogenic variants were p.Thr119Ile, p.Tyr159Cys, p.Leu282Pro, and p.Ala285Ser. Two patients had variants of unknown significance, p.Tyr389His and p.Tyr389Ser. EOFAD patients with PSEN1 variants showed early AD onset, frequent visuospatial dysfunction, movement disorders, and rapid disease progression. Brain MRIs revealed diffuse cortical atrophy, including parietal lobe atrophy, and/or hippocampal atrophy. FDG-PET scans also revealed significant hypometabolism in the bilateral temporo-parietal regions. Our findings provide insight to better understand the genetic background of Korean EOFAD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Amino Acid Sequence
  • Asian People / genetics*
  • Brain / diagnostic imaging
  • Brain / pathology
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuroimaging
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Positron-Emission Tomography
  • Presenilin-1 / chemistry
  • Presenilin-1 / genetics*
  • Republic of Korea

Substances

  • Presenilin-1

Supplementary concepts

  • Alzheimer disease, familial, type 3