Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP

Rita Joao Guerreiro, Miquel Baquero, Rafael Blesa, Mercè Boada, Jose Miguel Brás, Maria J. Bullido, Ana Calado, Richard Crook, Carla Ferreira, Ana Frank, Teresa Gómez-Isla, Isabel Hernández, Alberto Lleó, Alvaro Machado, Pablo Martínez-Lage, José Masdeu, Laura Molina-Porcel, José L. Molinuevo, Pau Pastor, Jordi Pérez-TurRute Relvas, Catarina Resende Oliveira, Maria Helena Ribeiro, Ekaterina Rogaeva, Alfredo Sa, Lluís Samaranch, Raquel Sánchez-Valle, Isabel Santana, Lluís Tàrraga, Fernando Valdivieso, Andrew Singleton, John Hardy, Jordi Clarimón

Research output: Contribution to journalArticlepeer-review

170 Scopus citations


Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset (<65years) Alzheimer's disease (AD). We performed a screening for mutations in the coding regions of presenilins, as well as exons 16 and 17 of the APP gene in a total of 231 patients from the Iberian peninsular with a clinical diagnosis of early-onset AD (mean age at onset of 52.9 years; range 31-64). We found three novel mutations in PSEN1, one novel mutation in PSEN2, and a novel mutation in the APP gene. Four previously described mutations in PSEN1 were also found. The same analysis was carried in 121 elderly healthy controls from the Iberian peninsular, and a set of 130 individuals from seven African populations belonging to the Centre d'Etude du Polymorphisme Humain-Human Genome Diversity Panel (CEPH-HGDP), in order to determine the extent of normal variability in these genes. Interestingly, in the latter series, we found five new non-synonymous changes in all three genes and a presenilin 2 variant (R62H) that has been previously related to AD. In some of these mutations, the pathologic consequence is uncertain and needs further investigation. To address this question we propose and use a systematic algorithm to classify the putative pathology of AD mutations.

Original languageEnglish (US)
Pages (from-to)725-731
Number of pages7
JournalNeurobiology of Aging
Issue number5
StatePublished - May 2010


  • APP
  • Early-onset Alzheimer's disease
  • Mutations
  • Presenilins

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology


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