title: Cognitively preserved subjects with transitional cerebrospinal fluid ß-amyloid 1-42 values have thicker cortex in Alzheimer's disease vulnerable areas.
abstract: BACKGROUND
  Establishing the relationship between cerebrospinal fluid (CSF) ß-amyloid 1-42 (Aß) and cortical thickness (CTh) would represent a major step forward in the understanding of the Alzheimer's disease (AD) process. We studied this relationship in a group of healthy control subjects and subjects with subjective memory complaints with preserved cognitive function at neuropsychological testing.
  
  
  METHODS
  In this cross-sectional study, 33 individuals (17 healthy control subjects and 16 subjects with subjective memory complaints) underwent structural 3-Tesla magnetic resonance image scanning and a spinal tap. Cerebrospinal fluid Aß was measured by enzyme-linked immunosorbent assay. The relationship between CSF Aß values and CTh in several regions of interest, both susceptible and unrelated to AD pathology, was analyzed with a curve fit analysis and CTh difference maps were derived from group comparisons.
  
  
  RESULTS
  Dichotomizing the whole sample according to Aß values (cutoff 500 pg/mL), we found the expected cortical thinning in Aß positive subjects in temporoparietal areas (p < .05 corrected). When analyzing the relationship between CSF Aß and CTh in AD-susceptible regions, we found a significant inverted U-shaped relationship (quadratic). Therefore, the sample was further divided into tertiles (according to CSF Aß values) to perform subsequent subgroup comparisons. Increased CTh in temporoparietal areas and precuneus (p < .05 corrected) was found in the middle Aß tertile (CSF Aß between 416 and 597 pg/mL) when compared with the high Aß tertile (616-881 pg/mL).
  
  
  CONCLUSIONS
  The relationship between Aß and CTh in preclinical stages may not be linear. Cortical thickness in temporoparietal and precuneus regions is greater in subjects with transitional CSF Aß values.
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fortea
authors.forename: Roser
authors.initials: R
authors.lastname: Sala-Llonch
authors.forename: David
authors.initials: D
authors.lastname: Bartrés-Faz
authors.forename: Albert
authors.initials: A
authors.lastname: Lladó
authors.forename: Cristina
authors.initials: C
authors.lastname: Solé-Padullés
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bosch
authors.forename: Anna
authors.initials: A
authors.lastname: Antonell
authors.forename: Jaume
authors.initials: J
authors.lastname: Olives
authors.forename: Raquel
authors.initials: R
authors.lastname: Sanchez-Valle
authors.forename: Jose L
authors.initials: JL
authors.lastname: Molinuevo
authors.forename: Lorena
authors.initials: L
authors.lastname: Rami
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001057:Apolipoproteins E / Q000235:genetics; D019540:Area Under Curve; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology*; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology*; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D007839:Functional Laterality; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)