Brain tissue metal concentrations and Alzheimer’s disease neuropathology in total joint arthroplasty patients versus controls

Blake A. Ebner, Sarah A. Erdahl, Carly S. Lundgreen, Maria Vassilaki, Walter K. Kremers, David S Knopman, Ronald C. Petersen, Daniel J. Berry, David G. Lewallen, Paul J. Jannetto, Melissa E Murray, R. Ross Reichard, Hilal Maradit Kremers

Research output: Contribution to journalArticlepeer-review

Abstract

We examined whether total joint arthroplasty (TJA) is associated with increased metal accumulation in the brain and histopathologic changes of Alzheimer’s disease. We measured ultra-trace metal concentrations (aluminum, chromium, cobalt, manganese, molybdenum, nickel, titanium, and vanadium) on postmortem frozen tissues of the occipital lobe of 177 subjects (89 non-TJA and 88 TJA) using a triple-quadrupole inductively coupled plasma mass spectrometry and correlated elemental concentrations to the degree of Alzheimer’s disease neuropathic change (ADNC). To effectively assess the relationship between TJA and brain metal concentrations, subjects with and without TJA were matched for baseline clinical characteristics and showed no difference in postmortem Alzheimer’s disease neuropathic change. TJA subjects had increased concentrations of cobalt and titanium and both metals were associated with increased amyloid plaques. In both the TJA and non-TJA subjects, increased concentrations of cobalt, titanium, manganese, and molybdenum were associated with increased odds of neuritic and diffuse plaques. Lastly, the brain’s inter-metal correlations were altered in the presence of increased neuritic plaques and/or implantable artificial joints. These findings suggest that metal concentrations and homeostasis vary in presence of TJA.

Original languageEnglish (US)
Article number18
JournalActa neuropathologica
Volume149
Issue number1
DOIs
StatePublished - Jun 2025

Keywords

  • Alzheimer disease pathology
  • Arthroplasty
  • Autopsy
  • Chromium
  • Cobalt
  • Titanium

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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