title: Genetic interaction of PICALM and APOE is associated with brain atrophy and cognitive impairment in Alzheimer's disease.
abstract: BACKGROUND
  Evidence has emerged indicating that the ε4 allele of APOE and PICALM interact in conferring risk of Alzheimer's disease (AD). The biologic basis of this interaction is unclear, but it is likely to have phenotypic relevance and contribute to the structural and clinical heterogeneity of AD.
  
  
  METHODS
  The aim of this study was to investigate interaction effects of the APOE ε4 allele and the alleles at the single-nucleotide polymorphism rs3851179 located in the PICALM locus. We analyzed brain volumes and cognitive phenotypes of 165 patients with early AD dementia.
  
  
  RESULTS
  There was a synergistic adverse effect of homozygosity for the PICALM risk allele G in rs3851179 and APOE ε4 on volume in prefrontal and performance on the Trail Making Test A, which is sensitive to processing speed and working memory function.
  
  
  CONCLUSIONS
  The data suggest a neural mechanism for APOE-PICALM interactions in patients with manifest AD and indicate that the PICALM genotype modulates both brain atrophy and cognitive performance in APOE ε4 carriers.
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Heidelberg, Germany. Electronic address: katrin.morgen@zi-mannheim.de.
authors.forename: Katrin
authors.initials: K
authors.lastname: Morgen
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ramirez
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Heidelberg, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Frölich
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Heidelberg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Tost
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Heidelberg, Germany.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Plichta
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Kölsch
authors.affiliation: Department of Medical Informatics, University of Göttingen, Göttingen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Rakebrandt
authors.affiliation: Department of Medical Informatics, University of Göttingen, Göttingen, Germany.
authors.forename: Otto
authors.initials: O
authors.lastname: Rienhoff
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Jessen
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Berlin, Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Peters
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Hamburg, Hamburg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Jahn
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Luckhaus
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Freiburg, Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hüll
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany.
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gertz
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Heidelberg, Heidelberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schröder
authors.affiliation: Département de Neurologie Institut de la Mémoire et de la Maladie d'Alzheimer, Université Pierre et Marie Curie, Hôpital de la Salpétriére Paris, France.
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Rostock, Rostock, Germany; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Teipel
authors.affiliation: Institute of General Practice, University of Frankfurt, Frankfurt, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Pantel
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Berlin, Berlin, Germany.
authors.forename: Isabella
authors.initials: I
authors.lastname: Heuser
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Essen, Essen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Wiltfang
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Rüther
authors.affiliation: Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases, Bonn, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer-Lindenberg
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology / Q000523:psychology; D001057:Apolipoproteins E / Q000235:genetics*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics*; D009483:Neuropsychological Tests; D009929:Organ Size; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D001057:Apolipoproteins E; D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human
keywords: APOE; Alzheimer's disease; Brain atrophy; Genetic interaction; PICALM