Affiliations: [a]
Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
| [b] MRC, Oulu University Hospital, Oulu, Finland
| [c]
Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit and Biocenter Oulu, University of Oulu, NordLab Oulu, Oulu, Finland
| [d]
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland
| [e]
Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
Correspondence:
[*]
Correspondence to: Anne M. Remes, MD, PhD, Professor, Dean, Faculty of Medicine, University of Oulu, Aapistie 5 A, FIN-90230 Oulu, Finland. Tel.: +358 50 533 0090; E-mail: anne.remes@oulu.fi.
Abstract: Background:Rare variants of SORL1 have been associated with an increased risk of early-onset or late-onset Alzheimer’s disease (AD). However, a lot remains to be clarified about their significance in the pathogenesis of the disease. Objective:To evaluate the role of SORL1 variants among Finnish patients with early-onset AD (EOAD). Methods:The rare SORL1variants were screened in a cohort of 115 Finnish EOAD patients (mean age at onset 58.3 years, range 46–65 years) by using the whole-exome sequencing. Results:We found one novel nonsense variant (p.Gln290*) and eight missense variants in SORL1. This is the first study reporting the SORL1 variants p.Lys80Arg, p.Ala789Val and p.Arg866Gln in EOAD patients. Furthermore, two of these three missense variants were overrepresented in EOAD patients compared to gnomAD non-neuro Finnish samples. Conclusion:This study strengthens the earlier findings, that the rare variants in SORL1 are associated with EOAD.
Keywords: Dementia, early onset Alzheimer’s disease, gene, human, mutation, neurodegenerative disease, single nucleotide polymorphism, SORL1
