title: Plasma amyloid-β levels are significantly associated with a transition toward Alzheimer's disease as measured by cognitive decline and change in neocortical amyloid burden.
abstract: BACKGROUND
  We evaluated the utility of longitudinal measures of plasma amyloid-β (Aβ) as a means to identify pre-symptomatic cognitive decline in Alzheimer's disease (AD) when coupled to neuroimaging and neuropsychological parameters.
  
  
  METHODS
  Participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were grouped based upon cognitive change and changes in measurable levels of neocortical amyloid over 36 months. Participants were classified as those who transitioned for cognitive decline and change in neocortical amyloid, those healthy controls that did not transition, and stable AD participants over 36 months.
  
  
  RESULTS
  Comparisons of plasma Aβ levels between the transition and non-transitional groups showed Aβ1-42 and the Aβ1-42/Aβ1-40 ratio were significantly decreased at baseline (p = 0.008 and p = 0.002, respectively) and at 18 months (p = 0.003 and p = 0.004, respectively). Both measures of neocortical amyloid and two previously published composite scores validated the creation of the novel transitional grouping (p < 0.0001). In addition Aβn-42 performed well as a longitudinal prognostic indicator of transition toward cognitive decline, with a significant decrease in the transition group at the 18 month time point (p = 0.01).
  
  
  CONCLUSIONS
  We demonstrated that baseline plasma Aβ1-42 and the Aβ1-42/Aβ1-40 ratio were putative biomarkers indicative of cognitive decline and validated this result using 18 month data. We created a novel transitional grouping and validated this measure using published measures of neocortical amyloid and composite memory scores. These findings suggest that longitudinal plasma Aβ could contribute to a pre-symptomatic biomarker panel for AD.
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
authors: Alan
authors: A
authors: Rembach
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
authors: Andrew D
authors: AD
authors: Watt
authors: CSIRO Mathematics, Informatics & Statistics, North Ryde, NSW, Australia.
authors: William J
authors: WJ
authors: Wilson
authors: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia.
authors: Victor L
authors: VL
authors: Villemagne
authors: CSIRO Preventative Health Flagship: Mathematics, Informatics and Statistics, Perth, WA, Australia.
authors: Samantha C
authors: SC
authors: Burnham
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia Department of Psychiatry, St. George's Hospital, University of Melbourne, VIC, Australia National Ageing Research Institute, Parkville, VIC, Australia.
authors: Kathryn A
authors: KA
authors: Ellis
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia CogState Ltd., Melbourne, VIC, Australia.
authors: Paul
authors: P
authors: Maruff
authors: National Ageing Research Institute, Parkville, VIC, Australia.
authors: David
authors: D
authors: Ames
authors: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia.
authors: Christopher C
authors: CC
authors: Rowe
authors: CSIRO Molecular and Health Technologies, Preventative Health Flagship, Parkville, VIC, Australia.
authors: S Lance
authors: SL
authors: Macaulay
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
authors: Ashley I
authors: AI
authors: Bush
authors: Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, WA, Australia.
authors: Ralph N
authors: RN
authors: Martins
authors: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
authors: Colin L
authors: CL
authors: Masters
authors: CSIRO Mathematics, Informatics & Statistics, North Ryde, NSW, Australia CSIRO Molecular and Health Technologies, Preventative Health Flagship, Parkville, VIC, Australia The Australian E-Health Research Centre, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
authors: James D
authors: JD
authors: Doecke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000150:complications*; D016229:Amyloid beta-Peptides / Q000097:blood*; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D019579:Neocortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D059906:Neuroimaging; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D013844:Thiazoles
keywords: Alzheimer's disease; Pittsburgh compound B; biomarkers; diagnosis; neocortical amyloid burden; plasma amyloid-β; positron emission topography