Blood metabolite markers of neocortical amyloid-β burden: discovery and enrichment using candidate proteins

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 plasm...

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Veröffentlicht in:Translational psychiatry Jg. 6; H. 1; S. e719
Hauptverfasser: Voyle, N, Kim, M, Proitsi, P, Ashton, N J, Baird, A L, Bazenet, C, Hye, A, Westwood, S, Chung, R, Ward, M, Rabinovici, G D, Lovestone, S, Breen, G, Legido-Quigley, C, Dobson, R J B, Kiddle, S J
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 26.01.2016
Nature Publishing Group
Schlagworte:
59/78
631/378/340
692/53/2423
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Aged
Alzheimer Disease - blood
Amyloid beta-Peptides - blood
Behavioral Sciences
Biological Psychology
Biomarkers - blood
Female
Humans
Male
Medicine
Medicine & Public Health
Middle Aged
Neocortex - metabolism
Neurosciences
Original
original-article
Pharmacotherapy
Psychiatry
ISSN:2158-3188, 2158-3188
Online-Zugang:Volltext
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Zusammenfassung: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.
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Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data, but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
Joint senior authors.
ISSN:2158-3188
2158-3188
DOI:10.1038/tp.2015.205