title: Hippocampal function in healthy carriers of the CLU Alzheimer's disease risk variant.
abstract: Alzheimer's disease is a devastating, common, progressive dementia with considerable heritability. Recently, a genetic variant associated with the disease was discovered at CLU (rs11136000) with genome-wide support. Here we show, using an imaging genetics approach in a large genotyped sample, that healthy carriers of the variant exhibit altered coupling between hippocampus and prefrontal cortex during memory processing, mirroring clinical evidence of disturbed connectivity in patients and providing a neurogenetic mechanism for CLU-associated risk and protection.
authors.affiliation: Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Mitte, D-11017 Berlin, Germany. susanne.erk@charite.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Erk
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer-Lindenberg
authors.forename: Carola
authors.initials: C
authors.lastname: Opitz von Boberfeld
authors.forename: Christine
authors.initials: C
authors.lastname: Esslinger
authors.forename: Knut
authors.initials: K
authors.lastname: Schnell
authors.forename: Peter
authors.initials: P
authors.lastname: Kirsch
authors.forename: Manuel
authors.initials: M
authors.lastname: Mattheisen
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Mühleisen
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Witt
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Henrik
authors.initials: H
authors.lastname: Walter
mesh_terms: D000328:Adult; D001931:Brain Mapping; D051152:Clusterin / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006624:Hippocampus / Q000098:blood supply / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017397:Prefrontal Cortex; D055815:Young Adult
chemical_list: C495242:CLU protein, human; D051152:Clusterin; D010100:Oxygen