title: Preclinical cerebrospinal fluid and volumetric magnetic resonance imaging biomarkers in Swedish familial Alzheimer's disease.
abstract: BACKGROUND
  It is currently believed that therapeutic interventions will be most effective when introduced at the preclinical stage of Alzheimer's disease (AD). This underlines the importance of biomarkers to detect AD pathology in vivo before clinical disease onset.
  
  
  OBJECTIVE
  To examine the evolution of cerebrospinal fluid (CSF) biomarker and brain structure changes in the preclinical phase of familial AD.
  
  
  METHODS
  The study included members from four Swedish families at risk for carrying an APPswe, APParc, PSEN1 H163Y, or PSEN1 I143T mutation. Magnetic resonance imaging (MRI) scans were obtained from 13 mutation carriers (MC) and 20 non-carriers (NC) and analyzed using vertex-based analyses of cortical thickness and volume. CSF was collected from 10 MC and 12 NC from familial AD families and analyzed for Aβ42, total tau (T-tau) and phospho-tau (P-tau).
  
  
  RESULTS
  The MC had significantly lower levels of CSF Aβ42 and higher levels T-tau and P-tau than the NC. There was a trend for a decrease in Aβ42 15-20 years before expected onset of clinical symptoms, while increasing T-tau and P-tau was not found until close to the expected clinical onset. The MC had decreased volume on MRI in the left precuneus, superior temporal gyrus, and fusiform gyrus.
  
  
  CONCLUSIONS
  Aberrant biomarker levels in CSF as well as regional brain atrophy are present in preclinical familial AD, several years before the expected onset of clinical symptoms.
authors.affiliation: Karolinska Institutet, Department NVS, Division of Neurogeriatrics, Center for Alzheimer Disease Research, Huddinge, Sweden Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Steinunn
authors.initials: S
authors.lastname: Thordardottir
authors.affiliation: Karolinska Institutet, Department NVS, Division of Neurogeriatrics, Center for Alzheimer Disease Research, Huddinge, Sweden Karolinska Institutet, Department of NVS, Division for Clinical Geriatrics, Center for Alzheimer Disease Research, Huddinge, Sweden.
authors.forename: Anne Kinhult
authors.initials: AK
authors.lastname: Ståhlbom
authors.affiliation: Karolinska Institutet, Department of NVS, Division for Clinical Geriatrics, Center for Alzheimer Disease Research, Huddinge, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: Karolinska Institutet, Department of NVS, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Huddinge, Sweden.
authors.forename: Ove
authors.initials: O
authors.lastname: Almkvist
authors.affiliation: Karolinska Institutet, Department of NVS, Division for Clinical Geriatrics, Center for Alzheimer Disease Research, Huddinge, Sweden.
authors.forename: Eric
authors.initials: E
authors.lastname: Westman
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden Karolinska Institutet, Department of NVS, Division for Clinical Geriatrics, Center for Alzheimer Disease Research, Huddinge, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Eriksdotter
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Karolinska Institutet, Department NVS, Division of Neurogeriatrics, Center for Alzheimer Disease Research, Huddinge, Sweden Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Graff
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D003071:Cognition; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009929:Organ Size; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D053764:Presenilin-1 / Q000235:genetics; D062706:Prodromal Symptoms; D013548:Sweden; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D015415:Biomarkers; C054369:MAPT protein, human; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer's disease; biomarkers; cerebrospinal fluid; genetics; magnetic resonance imaging; natural history studies; preclinical