E280A PS-1 mutation causes Alzheimer's disease but age of onset is not modified by ApoE alleles

Corinne L. Lendon, Alonso Martinez, Isabel Maria Behrens, Kenneth S. Kosik, Lucia Madrigal, Joanne Norton, Rosalind Neuman, Amanda Myers, Frances Busfield, Michelle Wragg, Mauricio Arcos, Juan Carlos Arango Viana, Jorge Ossa, Andres Ruiz, Alison M. Goate, Francisco Lopera

Research output: Contribution to journalArticle

69 Scopus citations


A single base substitution of a glutamic acid to an alanine codon 280 was found in the presenilin-1 (PS-1) gone on chromosome 14 in affected individuals in each of seven Colombian early-onset Alzheimer's disease (AD) kindreds. The mutation segregated with disease in kindreds tested. In the largest kindred (C2), the maximum two-point lod score between the mutation and AD was Z = 8.14 at Θ= 0. The presence of a single mutation and the common geographic origin, with all families from the state of Antioquia, suggest a founder effect in this population. This finding is supported by the observation of a rare haplotype inherited with AD in all kindreds. These kindreds form the largest collection of AD cases with the same PS-1 mutation and the same educational, environmental, and ethnic background in which to study the phenotypic effect of putative risk factors, such as the ε4 allele of apolipoprotein E (ApoE) or head trauma. Of the few AD cases having a history of head trauma, the age of onset was not lowered. No effect of ApoE genotype on the age of onset was detected. Previous investigations of the effect of ApoE genotype on the age of onset were confounded by small patient numbers, familial clustering of ApoE genotypes, and combining data from unrelated families with different mutations.

Original languageEnglish (US)
Pages (from-to)186-195
Number of pages10
JournalHuman mutation
Issue number3
StatePublished - Sep 15 1997
Externally publishedYes



  • Alzheimer's disease
  • Apolipoprotein E
  • Mutation
  • Presenilin-1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Lendon, C. L., Martinez, A., Behrens, I. M., Kosik, K. S., Madrigal, L., Norton, J., Neuman, R., Myers, A., Busfield, F., Wragg, M., Arcos, M., Viana, J. C. A., Ossa, J., Ruiz, A., Goate, A. M., & Lopera, F. (1997). E280A PS-1 mutation causes Alzheimer's disease but age of onset is not modified by ApoE alleles. Human mutation, 10(3), 186-195. https://doi.org/10.1002/(SICI)1098-1004(1997)10:3<186::AID-HUMU2>3.0.CO;2-H