title: Blood metabolite markers of neocortical amyloid-β burden: discovery and enrichment using candidate proteins.
abstract: We believe this is the first study to investigate associations between blood metabolites and neocortical amyloid burden (NAB) in the search for a blood-based biomarker for Alzheimer's disease (AD). Further, we present the first multi-modal analysis of blood markers in this field. We used blood plasma samples from 91 subjects enrolled in the University of California, San Francisco Alzheimer's Disease Research Centre. Non-targeted metabolomic analysis was used to look for associations with NAB using both single and multiple metabolic feature models. Five metabolic features identified subjects with high NAB, with 72% accuracy. We were able to putatively identify four metabolites from this panel and improve the model further by adding fibrinogen gamma chain protein measures (accuracy=79%). One of the five metabolic features was studied in the Alzheimer's Disease Neuroimaging Initiative cohort, but results were inconclusive. If replicated in larger, independent studies, these metabolic features and proteins could form the basis of a blood test with potential for enrichment of amyloid pathology in anti-amyloid trials.
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Voyle
authors.affiliation: Institute of Pharmaceutical Science, Kings College London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Proitsi
authors.affiliation: Department of Old Age Psychiatry, 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: N J
authors.initials: NJ
authors.lastname: Ashton
authors.affiliation: Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors.forename: A L
authors.initials: AL
authors.lastname: Baird
authors.affiliation: Department of Old Age Psychiatry, 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: C
authors.initials: C
authors.lastname: Bazenet
authors.affiliation: Department of Old Age Psychiatry, 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: A
authors.initials: A
authors.lastname: Hye
authors.affiliation: Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: Westwood
authors.affiliation: Proteomics Facility, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Chung
authors.affiliation: Proteomics Facility, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Ward
authors.affiliation: Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Rabinovici
authors.affiliation: Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Breen
authors.affiliation: Institute of Pharmaceutical Science, Kings College London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Legido-Quigley
authors.affiliation: NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
authors.forename: R J B
authors.initials: RJ
authors.lastname: Dobson
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Kiddle
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood*; D016229:Amyloid beta-Peptides / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers
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