title: The Relationship Between Plasma Aβ Levels, Cognitive Function and Brain Volumetrics: Sydney Memory and Ageing Study.
abstract: OBJECTIVE
  Determine whether (1) a relationship exists between plasma amyloid-β (Aβ)1- 40 and 1-42 peptide levels, brain volumetrics and cognitive performance in elderly individuals with and without amnestic mild cognitive impairment (aMCI), (2) plasma Aβ peptide levels differ between apolipoprotein E (APOE) ε4 carriers and non-carriers and (3) longitudinal changes in cognition and brain volume relate to Aβ levels.
  
  
  METHODS
  Subjects with aMCI (n = 89) and normal cognition (n = 126) were drawn from the Sydney Memory and Aging Study (Sydney MAS), a population based study of non-demented 70-90 year old individuals; 39 Alzheimer's disease (AD) patients were recruited from a specialty clinic. Sydney MAS participants underwent brain MRI scans and were assessed on 19 cognitive measures and were APOE ε4 genotyped. Plasma levels of Aβ1-40 and 1-42 were quantified using ELISA.
  
  
  RESULTS
  Wave1 plasma levels of Aβ peptides and Aβ1-42/1-40 ratio were lower in aMCI and AD, and Aβ1-42 was positively associated with global cognition and hippocampal volume and negatively with white matter hyperintensities. The relationships of Aβ1-40 and Aβ1-42 were predominantly observed in ε4 allele carriers and non-carriers respectively. Longitudinal analysis revealed greater decline in global cognition and memory for the highest quintiles of Aβ1-42 and the ratio measure.
  
  
  CONCLUSIONS
  Plasma Aβ levels and the Aβ1-42/1-40 ratio are related to cognition and hippocampal volumes, with differential associations of Aβ1-40 and Aβ1-42 in ε4 carriers and non-carriers. These data support the Aβ sink model of AD pathology, and suggest that plasma Aβ measures may serve as biomarkers of AD.
authors.affiliation: Bioanalytical Mass Spectrometry Facility, School of Medical Sciences, University of New South Wales, Sydney, Australia. a.poljak@unsw.edu.au.
authors.forename: Anne
authors.initials: A
authors.lastname: Poljak
authors.forename: John D
authors.initials: JD
authors.lastname: Crawford
authors.forename: George A
authors.initials: GA
authors.lastname: Smythe
authors.forename: Henry
authors.initials: H
authors.lastname: Brodaty
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Slavin
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Kochan
authors.forename: Julian N
authors.initials: JN
authors.lastname: Trollor
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
authors.forename: Karen A
authors.initials: KA
authors.lastname: Mather
authors.forename: Amelia A
authors.initials: AA
authors.lastname: Assareh
authors.forename: Pek C
authors.initials: PC
authors.lastname: Ng
authors.forename: Perminder S
authors.initials: PS
authors.lastname: Sachdev
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood* / Q000473:pathology*; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D016229:Amyloid beta-Peptides / Q000097:blood*; D053327:Apolipoprotein E4 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000473:pathology*; D003071:Cognition / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008568:Memory / Q000502:physiology*; D009517:New South Wales / Q000453:epidemiology; D009929:Organ Size; D010446:Peptide Fragments / Q000097:blood*
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)