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Molecular Genetic Analysis of the APP, PSEN1, and PSEN2 Genes in Finnish Patients With Early-onset Alzheimer Disease and Frontotemporal Lobar Degeneration

Krüger, Johanna MD*,†; Moilanen, Virpi MD, PhD*; Majamaa, Kari MD, PhD*,†; Remes, Anne M. MD, PhD*,†

Alzheimer Disease & Associated Disorders: July-September 2012 - Volume 26 - Issue 3 - p 272–276
doi: 10.1097/WAD.0b013e318231e6c7
Original Articles

Mutations in 3 genes, amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2), have been identified as causing a proportion of early-onset Alzheimer disease (eoAD) cases. A few PSEN mutations have also been previously detected in patients with frontotemporal lobar degeneration (FTLD). In order to evaluate the role of these genes in a clinical series of Finnish eoAD and FTLD patients, we sequenced exons 16 and 17 of the APP gene and the coding regions of the PSEN1 and PSEN2 genes in 140 eoAD and 66 FTLD patients. No pathogenic mutations were identified in the cohort. The E318G variant was detected with similar frequencies in the cases with eoAD and FTLD and the healthy controls, therefore, showing no association between E318G and eoAD. Furthermore, the PSEN2 R71W variant seems to be nonpathogenic, because it was present in our healthy controls. Mutations in the PSEN1, PSEN2, and APP genes seem to be rare in this population, as these genes exhibited no pathogenic mutations in our cohort of eoAD and FTLD patients even though about 40% of the cases were familial ones. This suggests the involvement of other, still unknown genetic factors in the pathogenesis of these diseases.

*Department of Clinical Medicine, Neurology, University of Oulu

Clinical Research Center, Oulu University Hospital, Oulu, Finland

Supported financially in part by grants from the Maire Taponen Foundation (J.K.) and the Orion-Farmos Research Foundation (J.K.), by clinical EVO grants from Oulu University Hospital (A.M.R., J.K.), the Finnish Medical Foundation (A.M.R.), the Päivikki and Sakari Sohlberg Foundation (A.M.R.), and Oulun Duodecim-Seura (A.M.R.).

The authors declare no conflict of interest.

Reprints: Anne M. Remes, MD, PhD, Department of Neurology, University of Oulu, Box 5000, FIN-90014 Oulu, Finland (e-mail:

Received November 2, 2010

Accepted August 3, 2011

© 2012 Lippincott Williams & Wilkins, Inc.