Cu, Fe and Zn isotope ratios in murine Alzheimer's disease models suggest specific signatures of amyloidogenesis and tauopathy

Nikolay Solovyev* (Corresponding Author), Ahmed H. El-Khatib, Marta Costas Rodríguez, Karima Schwab, Elizabeth Griffin, Andrea Raab, Bettina Platt, Franz Theuring, Jochen Vogl, Frank Vanhaecke* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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, 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 to those for the corresponding age- and gender-matched wild-type control mice (WT). Our data show that L66 brains showed significantly higher Fe levels than 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 in serum of L66 mice compared to WT. For 5xFAD mice, Zn exhibited a trend towards a lighter isotopic composition in brain and a heavier isotopic composition in serum compared to 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.
Original languageEnglish
Article number100292
Number of pages15
JournalThe Journal of Biological Chemistry
Volume296
Early online date13 Jan 2021
DOIs
Publication statusPublished - 2021

Keywords

  • Alzheimer’s disease
  • tau
  • amyloid-beta
  • copper
  • iron
  • zinc
  • multi-collector inductively coupled plasma-mass spectrometry (ICP-MS)
  • brain
  • serum
  • ISOTOPIC ANALYSIS
  • total element determination

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