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A plasma protein classifier for predicting amyloid burden for preclinical Alzheimer’s disease

Abstract:
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 participants. A protein classifier model was trained to predict Aβ-positive participants using feature selection and machine learning in AIBL and independently assessed in KARVIAH. A 12-feature model for predicting Aβ-positive participants was established and demonstrated high accuracy (testing area under the receiver operator characteristic curve = 0.891, sensitivity = 0.78, and specificity = 0.77). This extensive plasma proteomic study has unbiasedly highlighted putative and novel candidates for AD pathology that should be further validated with automated methodologies.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1126/sciadv.aau7220

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Psychiatry
Oxford college:
St Cross College
Role:
Author
ORCID:
0000-0001-9276-2720
More by this author
Role:
Author
ORCID:
0000-0003-3756-6430


Publisher:
American Association for the Advancement of Science
Journal:
Science Advances More from this journal
Volume:
5
Issue:
2
Article number:
eaau7220
Place of publication:
United States
Publication date:
2019-02-06
Acceptance date:
2018-12-19
DOI:
EISSN:
2375-2548
Pmid:
30775436


Language:
English
Keywords:
Pubs id:
974714
Local pid:
pubs:974714
Deposit date:
2020-03-20

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