Impact of aging on copper isotopic composition in the murine brain

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Title: Impact of aging on copper isotopic composition in the murine brain
Authors: Lahoud, Esther, Moynier, Frédéric, Luu, Tu-Han, Mahan, Brandon, Borgne, Marie Le
Contributors: lahoud-heilbronner, esther, Université Paris Cité, Equipe HAL, Institut de Physique du Globe de Paris (IPGP (UMR_7154)), Institut national des sciences de l'Univers (INSU - CNRS)-Université de La Réunion (UR)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, University of Melbourne, We thank Tu-Han Luu for her help with the mass-spectrometers laboratory at IPGP. E.L. thanks AAT for fundings. F.M. thanks the ERC for the POC Grant DAI (# 101081580). Parts of this work were supported by IPGP multidisciplinary program PARI, by Region Île-de-France SESAME grants no. 12015908, EX047016, and the IdEx Université de Paris grant, ANR-18-IDEX-0001, and the DIM ACAV+., ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018)
Source: Metallomics
Publisher Information: Oxford University Press (OUP), 2024.
Publication Year: 2024
Subject Terms: Male, 0301 basic medicine, Aging, MC–ICP–MS, [SDV]Life Sciences [q-bio], Inbred C57BL, metallomics, MESH: Brain, Mice, 03 medical and health sciences, Alzheimer Disease, [CHIM] Chemical Sciences, [CHIM]Chemical Sciences, Animals, Humans, MESH: Animals, MESH: Aging, copper isotopes, MC-ICP-MS, MESH: Mice, 0303 health sciences, MESH: Humans, aging, Brain, Alzheimer's disease, MESH: Male, MESH: Copper, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, biomarker, MESH: Alzheimer Disease, Copper
Description: Aging is the main risk factor for Alzheimer's disease (AD). AD is linked to alterations in metal homeostasis and changes in stable metal isotopic composition can occur, possibly allowing the latter to serve as relevant biomarkers for potential AD diagnosis. Copper stable isotopes are used to investigate changes in Cu homeostasis associated with various diseases. Prior work has shown that in AD mouse models, the accumulation of 63Cu in the brain is associated with the disease's progression. However, our understanding of how the normal aging process influences the brain's isotopic composition of copper remains limited. In order to determine the utility and predictive power of Cu isotopes in AD diagnostics, we aim—in this study—to develop a baseline trajectory of Cu isotopic composition in the normally aging mouse brain. We determined the copper concentration and isotopic composition in brains of 30 healthy mice (WT) ranging in age from 6 to 12 mo, and further incorporate prior data obtained for 3-mo-old healthy mice; this range approximately equates to 20–50 yr in human equivalency. A significant 65Cu enrichment has been observed in the 12-mo-old mice compared to the youngest group, concomitant with an increase in Cu concentration with age. Meanwhile, literature data for brains of AD mice display an enrichment in 63Cu isotope compared to WT. It is acutely important that this baseline enrichment in 65Cu is fully constrained and normalized against if any coherent diagnostic observations regarding 63Cu enrichment as a biomarker for AD are to be developed.
Document Type: Article
File Description: application/pdf
Language: English
ISSN: 1756-591X
DOI: 10.1093/mtomcs/mfae008
Access URL: https://pubmed.ncbi.nlm.nih.gov/38289854
https://hal.science/hal-04893528v1/document
https://doi.org/10.1093/mtomcs/mfae008
https://hal.science/hal-04893528v1
https://u-paris.hal.science/hal-04595594v1
https://doi.org/10.1093/mtomcs/mfae008
Rights: OUP Standard Publication Reuse
Accession Number: edsair.doi.dedup.....8b80317c5dea80b1d849c2b3fe522c7c
Database: OpenAIRE
Description
Abstract:Aging is the main risk factor for Alzheimer's disease (AD). AD is linked to alterations in metal homeostasis and changes in stable metal isotopic composition can occur, possibly allowing the latter to serve as relevant biomarkers for potential AD diagnosis. Copper stable isotopes are used to investigate changes in Cu homeostasis associated with various diseases. Prior work has shown that in AD mouse models, the accumulation of 63Cu in the brain is associated with the disease's progression. However, our understanding of how the normal aging process influences the brain's isotopic composition of copper remains limited. In order to determine the utility and predictive power of Cu isotopes in AD diagnostics, we aim—in this study—to develop a baseline trajectory of Cu isotopic composition in the normally aging mouse brain. We determined the copper concentration and isotopic composition in brains of 30 healthy mice (WT) ranging in age from 6 to 12 mo, and further incorporate prior data obtained for 3-mo-old healthy mice; this range approximately equates to 20–50 yr in human equivalency. A significant 65Cu enrichment has been observed in the 12-mo-old mice compared to the youngest group, concomitant with an increase in Cu concentration with age. Meanwhile, literature data for brains of AD mice display an enrichment in 63Cu isotope compared to WT. It is acutely important that this baseline enrichment in 65Cu is fully constrained and normalized against if any coherent diagnostic observations regarding 63Cu enrichment as a biomarker for AD are to be developed.
ISSN:1756591X
DOI:10.1093/mtomcs/mfae008