Origin of the PSEN1 E280A mutation causing early-onset Alzheimer's disease

Matthew A. Lalli, Hannah C. Cox, Mary L. Arcila, Liliana Cadavid, Sonia Moreno, Gloria Garcia, Lucia Madrigal, Eric M. Reiman, Mauricio Arcos-Burgos, Gabriel Bedoya, Mary E. Brunkow, Gustavo Glusman, Jared C. Roach, Leroy Hood, Kenneth S. Kosik, Francisco Lopera

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Background A mutation in presenilin 1 (E280A) causes early-onset Alzheimer's disease. Understanding the origin of this mutation will inform medical genetics.

Methods We sequenced the genomes of 102 individuals from Antioquia, Colombia. We applied identity-by-descent analysis to identify regions of common ancestry. We estimated the age of the E280A mutation and the local ancestry of the haplotype harboring this mutation.

Results All affected individuals share a minimal haplotype of 1.8 Mb containing E280A. We estimate a time to most recent common ancestor of E280A of 10 (95% credible interval, 7.2-12.6) generations. We date the de novo mutation event to 15 (95% credible interval, 11-25) generations ago. We infer a western European geographic origin of the shared haplotype.

Conclusions The age and geographic origin of E280A are consistent with a single founder dating from the time of the Spanish Conquistadors who began colonizing Colombia during the early 16th century.

Original languageEnglish
Pages (from-to)S277-S283.e10
JournalAlzheimer's and Dementia
Issue number5
StatePublished - 1 Oct 2014
Externally publishedYes


  • Alzheimer's disease
  • PSEN1
  • population genetics
  • whole-genome sequencing


Dive into the research topics of 'Origin of the PSEN1 E280A mutation causing early-onset Alzheimer's disease'. Together they form a unique fingerprint.

Cite this