title: Blood Protein Markers of Neocortical Amyloid-β Burden: A Candidate Study Using SOMAscan Technology.
abstract: BACKGROUND
  Four previously reported studies have tested for association of blood proteins with neocortical amyloid-β burden (NAB). If shown to be robust, these proteins could have utility as a blood test for enrichment in clinical trials of Alzheimer's disease (AD) therapeutics.
  
  
  OBJECTIVE
  This study aimed to investigate whether previously identified blood proteins also show evidence for association with NAB in serum samples from the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL). The study considers candidate proteins seen in cohorts other than AIBL and candidates previously discovered in the AIBL cohort.
  
  
  METHODS
  Our study used the SOMAscan platform for protein quantification in blood serum. Linear and logistic regressions were used to model continuous NAB and dichotomized NAB respectively using single proteins as a predictor. Multiple protein models were built using stepwise regression techniques and support vectors machines. Age and APOEɛ4 carriage were used as covariates for all analysis.
  
  
  RESULTS
  Of the 41 proteins previously reported, 15 AIBL candidates and 20 non-AIBL candidates were available for testing. Of these candidates, pancreatic polypeptide (PPY) and IgM showed a significant association with NAB. Notably, IgM was found to associate with continuous NAB across cognitively normal control subjects.
  
  
  CONCLUSIONS
  We have further demonstrated the association of PPY and IgM with NAB, despite technical differences between studies. There are several reasons for a lack of significance for the other candidates including platform differences and the use of serum rather than plasma samples. To investigate the possibility of technical differences causing lack of replication, further studies are required.
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|MRC Social, Genetic and Developmental Psychiatry Centre, King's College London, London, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Voyle
authors.affiliation: Janssen R&D, Neurosciences, Titusville, NJ, USA.
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.affiliation: CSIRO Digital Productivity and Food and Nutrition Flagships: eHealth, Floreat, WA, Australia.
authors.forename: Samantha C
authors.initials: SC
authors.lastname: Burnham
authors.affiliation: Janssen R&D, Neurosciences, Titusville, NJ, USA.
authors.forename: Antonia
authors.initials: A
authors.lastname: Covin
authors.affiliation: GE Global Research, Niskayuna, NY, USA.
authors.forename: Zhanpan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: GE Global Research, Niskayuna, NY, USA.
authors.forename: Dipen P
authors.initials: DP
authors.lastname: Sangurdekar
authors.affiliation: GE Global Research, Niskayuna, NY, USA.
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Tan Hehir
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
authors.forename: Chantal
authors.initials: C
authors.lastname: Bazenet
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Department of Psychiatry, Oxford University, Oxford, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|MRC Social, Genetic and Developmental Psychiatry Centre, King's College London, London, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Kiddle
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
authors.forename: Richard J B
authors.initials: RJ
authors.lastname: Dobson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000473:pathology; D000544:Alzheimer Disease / Q000097:blood* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D001315:Australia; D001798:Blood Proteins / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011506:Proteins; D040901:Proteomics; D013844:Thiazoles / Q000378:metabolism
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001057:Apolipoproteins E; D001798:Blood Proteins; D011506:Proteins; D013844:Thiazoles
keywords: Alzheimer’s disease; amyloid plaques; blood; positron emission tomography scan; proteomics