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Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort
Institute of Pharmaceutical Science, King's College London, London, UK; Steno Diabetes Center Copenhagen, Gentofte, Denmark.
Institute of Pharmaceutical Science, King's College London, London, UK; Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Biochemistry, University of Cambridge, Cambridge, UK.
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
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2019 (English)In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 15, no 6, p. 817-827Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers.

METHODS: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis.

RESULTS: Eight metabolites were associated with amyloid β and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory.

DISCUSSION: PFAMs have been found increased and associated with amyloid β burden in CSF and clinical measures.

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 15, no 6, p. 817-827
Keywords [en]
Alzheimer's disease, Amyloid, Biomarkers, Brain volume measurements, CSF, Cognitive function measurements, Dementia, EMIF-AD, Metabolomics, Tau
National Category
Medical and Health Sciences Neurology
Identifiers
URN: urn:nbn:se:oru:diva-79153DOI: 10.1016/j.jalz.2019.03.004ISI: 000470084500009PubMedID: 31078433Scopus ID: 2-s2.0-85066602218OAI: oai:DiVA.org:oru-79153DiVA, id: diva2:1385394
Note

Funding Agencies:

Innovative Medicines Initiative Joint Undertaking under EMIF, Grant number 115372

European Union (EU), Appeared in article as European Union

EFPIA companies  

European Commission Joint Research Centre, Appeared in article as European Commission, Grant number QLRT-2001-245537670

Department of Health of the Basque Government, Grant number  17.0.1.08.12.0000.2.454.01.41142.001.H

United States Department of Health & Human Services

National Institutes of Health (NIH) - USA, Appeared in article as National Institutes of Health, Grant number R15-GM107864

Available from: 2020-01-14 Created: 2020-01-14 Last updated: 2023-03-28Bibliographically approved

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Freund-Levi, Yvonne

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