@article{ce2b1d2fa1764261b4aac0324331b8e2,
title = "Association of SORL1 gene variants with Alzheimer's disease",
abstract = "SORL1 gene variants were described as risk factor of Alzheimer's disease (AD) additionally SORL1 gene variants were associated with altered Aβ42 CSF levels in AD patients. In the present study we investigated the association of SORL1 gene variants (rs2070045 (SNP19), SORL1-18ex26 (SNP21), rs3824968 (SNP23), rs1010159 (SNP25)) with AD risk by using Cox proportional hazard model and Kaplan-Meier survival analysis in 349 AD patients and 483 controls, recruited from a multicenter study of the German Competence Network Dementias. The SNP21G-allele and a SORL1 haplotype consisting of the SNP19 T-allele, SNP21 G-allele and SNP23 A-allele (T/G/A) were associated with increased hazard ratios and an earlier age at onset of AD (SNP21: p = 0.002; T/G/A haplotype: p = 0.007). This effect was most pronounced in carriers of an additional APOE4 allele (SNP21: p = 0.003; T/G/A haplotype: p = 0.005). In conclusion, we found SORL1 gene variants located in the 3′ region of the gene to be associated with increased AD risk and an earlier age at onset of AD in our Central-European population. Thus, our data support a role of SORL1 polymorphisms in AD.",
keywords = "Age at onset, Alzheimer dementia, Association, SORL1",
author = "Heike K{\"o}lsch and Frank Jessen and Jens Wiltfang and Piotr Lewczuk and Martin Dichgans and Teipel, {Stefan J.} and Johannes Kornhuber and Lutz Fr{\"o}lich and Isabella Heuser and Oliver Peters and Birgitt Wiese and Hanna Kaduszkiewicz and {van den Bussche}, Hendrik and Michael H{\"u}ll and Alexander Kurz and Eckhart R{\"u}ther and Henn, {Fritz A.} and Wolfgang Maier",
note = "Funding Information: Healthy controls of comparable mean age and age range as AD patients (n = 483, mean age: 71.56 years, 52.1% female) were recruited in a prospective longitudinal study in general practitioner practices in six study centres (Hamburg, Bonn, D{\"u}sseldorf, Leipzig, Mannheim and Munich), in 12 German gerontopsychiatric university departments (funded by the German Competence Network Dementia) and with the support of the local Census Bureau and the regional Board of Data protection (Nordrhein-Westfalen, Germany). Probands were diagnosed by structured interviews and neuropsychological testing. Subjects with cognitive impairment as defined by the Structured Interview for Diagnosis of Dementia of Alzheimer type, Multi-infarct Dementia and Dementia of other Etiology according to DSM-IV and ICD-10 (SIDAM; Zaudig et al., 1991 ) were excluded. All control subjects and patients or their legal guardians gave informed consent for participation in the study. The study was approved by the ethics committees of all the participating universities. Funding Information: This study is part of the German Dementia Competence Network and was funded by the German Federal Ministry for Education and Research (grant: 01GI0422). We thank the anonymous reviewer for his helpful comments which substantially contributed to the study. We thank Beisa Burnic, Christine Frahnert-Ledschbor, Sandra Schmitz and Anne Schulz for skilful technical assistance.",
year = "2009",
month = apr,
day = "6",
doi = "10.1016/j.brainres.2009.01.044",
language = "English",
volume = "1264",
pages = "1--6",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
}