A plasma protein classifier for predicting amyloid burden for preclinical Alzheimer's disease.
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ABSTRACT:
SUBMITTER: Ashton NJ
PROVIDER: S-EPMC6365111 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
Publications
A plasma protein classifier for predicting amyloid burden for preclinical Alzheimer's disease.
Ashton Nicholas J NJ Nevado-Holgado Alejo J AJ Barber Imelda S IS Lynham Steven S Gupta Veer V Chatterjee Pratishtha P Goozee Kathryn K Hone Eugene E Pedrini Steve S Blennow Kaj K Schöll Michael M Zetterberg Henrik H Ellis Kathryn A KA Bush Ashley I AI Rowe Christopher C CC Villemagne Victor L VL Ames David D Masters Colin L CL Aarsland Dag D Powell John J Lovestone Simon S Martins Ralph R Hye Abdul A
Science advances 20190206 2
A blood-based assessment of preclinical disease would have huge potential in the enrichment of participants for Alzheimer's disease (AD) therapeutic trials. In this study, cognitively unimpaired individuals from the AIBL and KARVIAH cohorts were defined as Aβ negative or Aβ positive by positron emission tomography. Nontargeted proteomic analysis that incorporated peptide fractionation and high-resolution mass spectrometry quantified relative protein abundances in plasma samples from all particip ...[more]
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Project description:IntroductionThe typical spatial pattern of amyloid-β (Aβ) in diagnosed Alzheimer's disease (AD) is that of a symmetrical hemispheric distribution. However, Aβ may be asymmetrically distributed in early stages of AD. Aβ distribution on PET has previously been explored in MCI and AD, but it has yet to be directly investigated in preclinical AD (pAD). We examined how Aβ was distributed in individuals with pAD and MCI using 11C-Pittsburgh Compound B (PiB) PET.MethodsIn this PET study, 79 subjects were retrospectively enrolled, including 34 controls, 24 pAD, and 21 MCI. All subjects underwent APOE genotyping, 11C-PiB PET, MRI, and cognitive testing. We explored differences in Aβ load, Aβ lateralisation, and Aβ distribution, as well as associations between Aβ distribution and cognition.ResultsThe Aβ asymmetry index (AI) differed between groups, with pAD having the highest Aβ AI as compared to both controls and MCI. There was no clear Aβ lateralisation in pAD, but there was a non-significant trend towards Aβ being more left-lateralised in MCI. There were no correlations between the cognitive scores and Aβ AI or Aβ lateralisation in pAD or MCI.ConclusionThe distribution of Aβ is most asymmetrical in pAD, as Aβ first starts accumulating, and it then becomes less asymmetrical in MCI, when Aβ has spread further, suggesting that more pronounced asymmetrical Aβ distribution may be a distinguishing factor in pAD. Longitudinal studies examining the distribution of Aβ across the AD continuum are needed.
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