Human fibroblast and stem cell resource from the Dominantly Inherited Alzheimer Network

Alzheimers Res Ther. 2018 Jul 25;10(1):69. doi: 10.1186/s13195-018-0400-0.

Abstract

Background: Mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) cause autosomal dominant forms of Alzheimer disease (ADAD). More than 280 pathogenic mutations have been reported in APP, PSEN1, and PSEN2. However, understanding of the basic biological mechanisms that drive the disease are limited. The Dominantly Inherited Alzheimer Network (DIAN) is an international observational study of APP, PSEN1, and PSEN2 mutation carriers with the goal of determining the sequence of changes in presymptomatic mutation carriers who are destined to develop Alzheimer disease.

Results: We generated a library of 98 dermal fibroblast lines from 42 ADAD families enrolled in DIAN. We have reprogrammed a subset of the DIAN fibroblast lines into patient-specific induced pluripotent stem cell (iPSC) lines. These cells were thoroughly characterized for pluripotency markers.

Conclusions: This library represents a comprehensive resource that can be used for disease modeling and the development of novel therapeutics.

Keywords: Amyloid precursor protein; Dominantly Inherited Alzheimer Network; Fibroblasts; Induced pluripotent stem cells; Presenilin 1; Presenilin 2.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Protein Precursor / genetics
  • Databases, Factual / statistics & numerical data
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Humans
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / pathology
  • Information Services
  • International Cooperation
  • Karyotyping
  • Male
  • Middle Aged
  • Mutation / genetics
  • Presenilin-1 / genetics
  • Presenilin-2 / genetics
  • Stem Cells / metabolism
  • Stem Cells / pathology*
  • Transduction, Genetic

Substances

  • Amyloid beta-Protein Precursor
  • Presenilin-1
  • Presenilin-2