Longitudinal biometal accumulation and Ca isotope composition of the Göttingen minipig brain

Mahan, Brandon, Antonelli, Michael A., Burckel, Pierre, Turner, Simon, Chung, Roger, Habekost, Mette, Jørgensen, Arne Lund, and Moynier, Frédéric (2020) Longitudinal biometal accumulation and Ca isotope composition of the Göttingen minipig brain. Metallomics, 12 (10). pp. 1585-1598.

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Abstract

Biometals play a critical role in both the healthy and diseased brain's functioning. They accumulate in the normal aging brain, and are inherent to neurodegenerative disorders and their associated pathologies. A prominent example of this is the brain accumulation of metals such as Ca, Fe and Cu (and more ambiguously, Zn) associated with Alzheimer's disease (AD). The natural stable isotope compositions of such metals have also shown utility in constraining biological mechanisms, and in differentiating between healthy and diseased states, sometimes prior to conventional methods. Here we have detailed the distribution of the biologically relevant elements Mg, P, K, Ca, Fe, Cu and Zn in brain regions of Göttingen minipigs ranging in age from three months to nearly six years, including control animals and both a single- and double-transgenic model of AD (PS1, APP/PS1). Moreover, we have characterized the Ca isotope composition of the brain for the first time. Concentration data track rises in brain biometals with age, namely for Fe and Cu, as observed in the normal ageing brain and in AD, and biometal data point to increased soluble amyloid beta (Aβ) load prior to AD plaque identification via brain imaging. Calcium isotope results define the brain as the isotopically lightest permanent reservoir in the body, indicating that brain Ca dyshomeostasis may induce measurable isotopic disturbances in accessible downstream reservoirs such as biofluids.

Item ID: 65704
Item Type: Article (Research - C1)
ISSN: 1756-591X
Keywords: Isotope metallomics, Alzheimer's disease, Trace elements
Copyright Information: © The Royal Society of Chemistry 2020
Funders: European Research Council (ERC), Institut de Physique du Globe de Paris (IDGP), Region-ile-de-France SESAME (RDFS), Macquarie University (MQ)
Projects and Grants: ERC European Community's H2020 framework program, ERC grant agreement #637503, IDGP multi-disciplinary program PARI, RDFS grant 12015908, MQ Deputy Vice Chancellor discretionary funds
Date Deposited: 16 Feb 2021 01:43
FoR Codes: 34 CHEMICAL SCIENCES > 3402 Inorganic chemistry > 340201 Bioinorganic chemistry @ 50%
46 INFORMATION AND COMPUTING SCIENCES > 4606 Distributed computing and systems software > 460606 Energy-efficient computing @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920112 Neurodegenerative Disorders Related to Ageing @ 100%
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