A novel PSEN1 mutation (I238M) associated with early-onset Alzheimer's disease in an African-American woman

J Alzheimers Dis. 2014;40(2):271-5. doi: 10.3233/JAD-131844.


Mutations in PSEN1 are the most common cause of autosomal dominant familial Alzheimer's disease (FAD). We describe an African-American woman with a family history consistent with FAD who began to experience cognitive decline at age 50. Her clinical presentation, MRI, FDG-PET, and PIB-PET scan findings were consistent with AD and she was found to have a novel I238M substitution in PSEN1. As this mutation caused increased production of Aβ42 in an in vitro assay, was not present in two population databases, and is conserved across species, it is likely to be pathogenic for FAD.

Keywords: African; Alzheimer's disease; PIB-PET; PSEN1; amyloid-β$_{42}$; autosomal dominant; familial; gamma-secretase; in vitro; presenilin-1.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Americans
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics*
  • Aniline Compounds
  • Benzothiazoles
  • Brain / diagnostic imaging
  • Brain / pathology
  • Female
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Isoleucine / genetics*
  • Methionine / genetics*
  • Middle Aged
  • Mutation / genetics*
  • Positron-Emission Tomography
  • Presenilin-1 / genetics*
  • Thiazoles
  • Transfection


  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Aniline Compounds
  • Benzothiazoles
  • PSEN1 protein, human
  • Presenilin-1
  • Thiazoles
  • Isoleucine
  • Green Fluorescent Proteins
  • Methionine