title: Evolving brain functional abnormalities in PSEN1 mutation carriers: a resting and visual encoding fMRI study.
abstract: PSEN1 mutations are the most frequent cause of familial Alzheimer's disease and show nearly full penetrance. Here we studied alterations in brain function in a cohort of 19 PSEN1 mutation carriers: 8 symptomatic (SMC) and 11 asymptomatic (AMC). Asymptomatic carriers were, on average, 12 years younger than the predicted age of disease onset. Thirteen healthy subjects were used as a control group (CTR). Subjects underwent a 10-min resting-state functional magnetic resonance imaging (fMRI) scan and also performed a visual encoding task. The analysis of resting-state fMRI data revealed alterations in the default mode network, with increased frontal connectivity and reduced posterior connectivity in AMC and decreased frontal and increased posterior connectivity in SMC. During task-related fMRI, SMC showed reduced activity in regions of the left occipital and left prefrontal cortices, while both AMC and SMC showed increased activity in a region within the precuneus/posterior cingulate, all as compared to CTR. Our findings suggest that fMRI can detect evolving changes in brain mechanisms in PSEN1 mutation carriers and support the use of this technique as a biomarker in Alzheimer's disease, even before the appearance of clinical symptoms.
authors.affiliation: Department of Psychiatry and Clinical Psychobiology, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Sala-Llonch
authors.forename: Juan
authors.initials: J
authors.lastname: Fortea
authors.forename: David
authors.initials: D
authors.lastname: Bartrés-Faz
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bosch
authors.forename: Albert
authors.initials: A
authors.lastname: Lladó
authors.forename: Cleofé
authors.initials: C
authors.lastname: Peña-Gómez
authors.forename: Anna
authors.initials: A
authors.lastname: Antonell
authors.forename: Fernando
authors.initials: F
authors.lastname: Castellanos-Pinedo
authors.forename: Nuria
authors.initials: N
authors.lastname: Bargalló
authors.forename: José Luis
authors.initials: JL
authors.lastname: Molinuevo
authors.forename: Raquel
authors.initials: R
authors.lastname: Sánchez-Valle
mesh_terms: D000328:Adult; D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology; D019943:Amino Acid Substitution / Q000235:genetics; D058070:Asymptomatic Diseases; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D005260:Female; D059907:Functional Neuroimaging; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D053764:Presenilin-1 / Q000235:genetics*; D013647:Task Performance and Analysis
chemical_list: C508853:PSEN1 protein, human; D053764:Presenilin-1