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Molecular diagnosis of autosomal dominant early onset Alzheimer’s disease: an update
  1. G Raux1,
  2. L Guyant-Maréchal2,
  3. C Martin2,
  4. J Bou1,
  5. C Penet3,
  6. A Brice3,
  7. D Hannequin4,
  8. T Frebourg2,
  9. D Campion1
  1. 1Inserm U 614, IFRMP, Faculty of Medicine, Rouen, France
  2. 2Department of Genetics, Rouen University Hospital, France
  3. 3Inserm U 679, Salpêtrière Hospital, Paris, France
  4. 4Department of Neurology, Rouen University Hospital
  1. Correspondence to:
 Dr D Campion
 Inserm U614, Faculty of Medicine, IFRMP, 22 Boulevard Gambetta, 76183 Rouen, France;


Background: Autosomal dominant early onset Alzheimer’s disease (ADEOAD) is genetically heterogeneous. Mutations of the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes have been identified.

Objective: To further clarify the respective contribution of these genes to ADEOAD.

Methods: 31 novel families were investigated. They were ascertained using stringent criteria (the occurrence of probable or definite cases of Alzheimer’s disease with onset before 60 years of age in three generations). All cases fulfilled the NINCDS-ADRDA criteria for probable or definite Alzheimer’s disease. The entire coding regions of PSEN1 and PSEN2 genes and exons 16 and 17 of APP gene were sequenced from genomic DNA

Results:PSEN1 mutations, including eight previously unreported mutations, were detected in 24 of the 31 families, and APP mutations were found in five families. In this sample, the mean ages of disease onset in PSEN1 and APP mutation carriers were 41.7 and 51.2 years, respectively.

Conclusions: Combining these data with previously published data, yielding 65 ADEOAD families, 66% of the cases were attributable to PSEN1 mutations and 16% to APP mutations, while 18% remained unexplained.

  • ADEOAD, autosomal dominant early onset Alzheimer’s disease
  • NINCDS-ADRDA, National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association
  • autosomal dominant early onset Alzheimer’s disease
  • PSEN1
  • PSEN2
  • APP

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  • Additional data including pedigree structures are available from the corresponding author upon request.

  • Competing interests: none declared