title: Evolving brain structural changes in PSEN1 mutation carriers.
abstract: Familial Alzheimer's disease provides the opportunity to investigate brain changes even before the symptoms onset. We performed a structural magnetic resonance imaging (MRI) study in 38 participants from families with presenilin 1 gene mutations: 11 symptomatic mutation carriers, 13 asymptomatic mutation carriers (AMC), with a mean of 16.22 years before the estimated appearance of symptoms, and 14 noncarriers. A subset of subjects was studied longitudinally 2 and 4 years after the first scan. We found decreased cortical thickness (CTh) and volume in cortical and subcortical structures in symptomatic mutation carriers, with progressive loss over time. In AMC, we found increased CTh and volume in temporoparietal regions and in precuneus-posterior cingulate compared with controls at baseline. Longitudinal studies in AMC, by contrast, showed accelerated rates of CTh loss in precuneus-posterior cingulate and superior parietal, right lateral temporal and left orbitofrontal, and middle frontal regions. These findings suggest that brain structure in presenilin 1 mutation carriers follows nonlinear trajectories, with regional increases during the very early presymptomatic period. Initial neuroinflammation and/or accumulation of amyloid species followed by neurodegeneration, or congenital morphometric differences, may explain the observed features.
authors: Department of Psychiatry and Clinical Psychobiology, Universitat de Barcelona, Barcelona, Spain; Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors: Roser
authors: R
authors: Sala-Llonch
authors: Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, Barcelona, Spain.
authors: Albert
authors: A
authors: Lladó
authors: Memory Unit, Department of Neurology, Hospital de Sant Pau, Barcelona, Spain.
authors: Juan
authors: J
authors: Fortea
authors: Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, Barcelona, Spain.
authors: Beatriz
authors: B
authors: Bosch
authors: Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, Barcelona, Spain.
authors: Anna
authors: A
authors: Antonell
authors: Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, Barcelona, Spain.
authors: Mircea
authors: M
authors: Balasa
authors: Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Radiology, Hospital Clínic, Barcelona, Spain.
authors: Nuria
authors: N
authors: Bargalló
authors: Department of Psychiatry and Clinical Psychobiology, Universitat de Barcelona, Barcelona, Spain; Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors: David
authors: D
authors: Bartrés-Faz
authors: Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, Barcelona, Spain.
authors: José Luis
authors: JL
authors: Molinuevo
authors: Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, Barcelona, Spain. Electronic address: rsanchez@clinic.ub.es.
authors: Raquel
authors: R
authors: Sánchez-Valle
mesh_terms: D000328:Adult; D058070:Asymptomatic Diseases; D002540:Cerebral Cortex / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006579:Heterozygote; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009929:Organ Size / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: C508853:PSEN1 protein, human; D053764:Presenilin-1
keywords: Alzheimer's disease; Biomarkers; Cortical thickness; Presenilin 1; Presymptomatic