Cu, Fe, and Zn isotope ratios in murine Alzheimer's disease models suggest specific signatures of amyloidogenesis and tauopathy.
Alzheimer Disease
/ genetics
Amyloid beta-Protein Precursor
/ genetics
Animals
Copper
/ metabolism
Disease Models, Animal
Gene Expression
Iron
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutation
Phosphorylation
Presenilin-1
/ genetics
Protein Aggregates
/ genetics
Spectrophotometry, Atomic
Transgenes
Zinc
/ metabolism
tau Proteins
/ genetics
Alzheimer’s disease
amyloid-beta
brain
copper
iron
isotopic analysis
multicollector inductively coupled plasma–mass spectrometry (ICP-MS)
serum
tau
zinc
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
Historique:
received:
21
06
2020
revised:
06
01
2021
accepted:
11
01
2021
pubmed:
17
1
2021
medline:
1
9
2021
entrez:
16
1
2021
Statut:
ppublish
Résumé
Alzheimer's disease (AD) is characterized by accumulation of tau and amyloid-beta in the brain, and recent evidence suggests a correlation between associated protein aggregates and trace elements, such as copper, iron, and zinc. In AD, a distorted brain redox homeostasis and complexation by amyloid-beta and hyperphosphorylated tau may alter the isotopic composition of essential mineral elements. Therefore, high-precision isotopic analysis may reveal changes in the homeostasis of these elements. We used inductively coupled plasma-mass spectrometry (ICP-MS)-based techniques to determine the total Cu, Fe, and Zn contents in the brain, as well as their isotopic compositions in both mouse brain and serum. Results for male transgenic tau (Line 66, L66) and amyloid/presenilin (5xFAD) mice were compared with those for the corresponding age- and sex-matched wild-type control mice (WT). Our data show that L66 brains showed significantly higher Fe levels than did those from the corresponding WT. Significantly less Cu, but more Zn was found in 5xFAD brains. We observed significantly lighter isotopic compositions of Fe (enrichment in the lighter isotopes) in the brain and serum of L66 mice compared with WT. For 5xFAD mice, Zn exhibited a trend toward a lighter isotopic composition in the brain and a heavier isotopic composition in serum compared with WT. Neither mouse model yielded differences in the isotopic composition of Cu. Our findings indicate significant pathology-specific alterations of Fe and Zn brain homeostasis in mouse models of AD. The associated changes in isotopic composition may serve as a marker for proteinopathies underlying AD and other types of dementia.
Identifiants
pubmed: 33453282
pii: S0021-9258(21)00060-0
doi: 10.1016/j.jbc.2021.100292
pmc: PMC7949056
pii:
doi:
Substances chimiques
APP protein, human
0
Amyloid beta-Protein Precursor
0
MAPT protein, human
0
PSEN1 protein, human
0
Presenilin-1
0
Protein Aggregates
0
tau Proteins
0
Copper
789U1901C5
Iron
E1UOL152H7
Zinc
J41CSQ7QDS
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100292Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare no conflict of interest.
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