University of Oulu

Laura Luukkainen, Seppo Helisalmi, Laura Kytövuori, Riitta Ahmasalo, Eino Solje, Annakaisa Haapasalo, … Johanna Krüger. (2019). Mutation Analysis of the Genes Linked to Early Onset Alzheimer’s Disease and Frontotemporal Lobar Degeneration. Journal of Alzheimer’s Disease, 69(3), 775–782.

Mutation analysis of the genes linked to early onset Alzheimer's disease and frontotemporal lobar degeneration

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Author: Luukkainen, Laura1,2; Helisalmi, Seppo3; Kytövuori, Laura1,2;
Organizations: 1Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
2MRC, Oulu University Hospital, Oulu, Finland
3Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland
4Department of Neurology, Lapland Central Hospital, Rovaniemi, Finland
5Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland
6A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland
7Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.4 MB)
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Language: English
Published: IOS Press, 2019
Publish Date: 2019-09-23


A lot of effort has been done to unravel the genetics underlying early-onset Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). However, many familial early-onset dementia (EOD) cases still show an unclear genetic background. The aim of this study was to evaluate the role of the known causative mutations and possible pathogenic variants associated with AD and FTLD in a Finnish EOD cohort. The cohort consisted of 39 patients (mean age at onset 54.8 years, range 39–65) with a positive family history of dementia or an atypical or rapidly progressive course of the disease. None of the patients carried the C9orf72 hexanucleotide repeat expansion. Mutations and variants in APP, PSEN1, PSEN2, MAPT, GRN, VCP, CHMP2B, FUS, TARDBP, TREM2, TMEM106B, UBQLN2, SOD1, PRNP, UBQLN1, and BIN1 were screened by using a targeted next generation sequencing panel. Two previously reported pathogenic mutations (PSEN1 p.His163Arg and MAPT p.Arg406Trp) were identified in the cohort. Both patients had familial dementia with an atypical early onset phenotype. In addition, a heterozygous p.Arg71Trp mutation in PSEN2 with an uncertain pathogenic nature was identified in a patient with neuropathologically confirmed AD. In conclusion, targeted investigation of the known dementia-linked genes is worthwhile in patients with onset age under 55 and a positive family history, as well as in patients with atypical features.

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Series: Journal of Alzheimer's disease
ISSN: 1387-2877
ISSN-E: 1875-8908
ISSN-L: 1387-2877
Volume: 69
Issue: 3
Pages: 775 - 782
DOI: 10.3233/JAD-181256
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
Funding: This study was supported by brain research grant from University of Oulu (LL, AMR), the Finnish Brain Foundation (ES), Academy of Finland (no 307866, MH; no 315459, AH; no 315460, AMR), and Sigrid Jusélius Foundation (MH), and the Strategic Neuroscience Funding of the University of Eastern Finland (MH; AH).
Academy of Finland Grant Number: 307866
Detailed Information: 307866 (Academy of Finland Funding decision)
315459 (Academy of Finland Funding decision)
315460 (Academy of Finland Funding decision)
Copyright information: © 2017 IOS Press. The Version of Record can be found at: