title: Influence of genetic variants in SORL1 gene on the manifestation of Alzheimer's disease.
abstract: We studied the association of SORL1 single-nucleotide polymorphisms genotypes with measures of pathology in patients with probable Alzheimer's disease (AD) using an endophenotype approach. We included (1) 133 patients from the German Dementia Competence Network (71 ± 8 years; 50% females; Mini Mental State Examination [MMSE], 24 ± 3); (2) 83 patients from the Alzheimer's Disease Neuroimaging Initiative (75 ± 8 years; 45% females; MMSE, 24 ± 2); and (3) 452 patients from the Amsterdam Dementia Cohort 66 ± 8 years; 47% females; MMSE, 20 ± 5). As endophenotype markers we used cognitive tests, cerebrospinal fluid (CSF) biomarkers amyloid-beta, total tau (tau), tau phosphorylated at threonine 181, and hippocampal atrophy. We measured 19 SORL1 SNP alleles. Genotype-endophenotype associations were determined by linear regression analyses. There was an association between rs2070045-G allele and increased CSF-tau and more hippocampal atrophy. Additionally, haplotype-based analyses revealed an association between haplotype rs11218340-A/rs3824966-G/rs3824968-A and higher CSF-tau and CSF-tau phosphorylated at threonine 181. In conclusion, we found that SORL1 SNP rs2070045-G allele was related to CSF-tau and hippocampal atrophy, 2 endophenotype markers of AD, suggesting that SORL1 may be implicated in the downstream pathology in AD.
authors: Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands. Electronic address: e.louwersheimer@vumc.nl.
authors: Eva
authors: E
authors: Louwersheimer
authors: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors: Alfredo
authors: A
authors: Ramirez
authors: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors: Carlos
authors: C
authors: Cruchaga
authors: German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
authors: Tim
authors: T
authors: Becker
authors: Department of Psychiatry and Psychotherapy, Friedrich-Alexander University of Erlangen, Nuremberg, Germany.
authors: Johannes
authors: J
authors: Kornhuber
authors: Department of Psychiatry, Charite, Berlin, Germany.
authors: Oliver
authors: O
authors: Peters
authors: Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
authors: Stefanie
authors: S
authors: Heilmann
authors: Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
authors: Jens
authors: J
authors: Wiltfang
authors: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors: Frank
authors: F
authors: Jessen
authors: Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands; Department of Psychiatry and Neuropsychology, Alzheimer Centre Limburg, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors: Pieter Jelle
authors: PJ
authors: Visser
authors: Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors: Philip
authors: P
authors: Scheltens
authors: Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors: Yolande A L
authors: YA
authors: Pijnenburg
authors: Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors: Charlotte E
authors: CE
authors: Teunissen
authors: Department of Radiology, VU University Medical Center, Amsterdam, the Netherlands.
authors: Frederik
authors: F
authors: Barkhof
authors: Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Clinical Genetics, VU University Medical Center, Amsterdam, the Netherlands.
authors: John C
authors: JC
authors: van Swieten
authors: Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands; Department of Clinical Genetics, VU University Medical Center, Amsterdam, the Netherlands.
authors: Henne
authors: H
authors: Holstege
authors: Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
authors: Wiesje M
authors: WM
authors: Van der Flier
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000577:Amides; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D010756:Phosphoric Acids; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D000577:Amides; D016229:Amyloid beta-Peptides; D015415:Biomarkers; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; D010756:Phosphoric Acids; C102582:SORL1 protein, human; D016875:tau Proteins; C011067:phosphoramidic acid
keywords: Alzheimer's disease; Endophenotypes; SNPs; SORL1