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. 2025 Feb 15;149(1):18.
doi: 10.1007/s00401-025-02856-9.

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

Blake A Ebner  1 , Sarah A Erdahl  1 , Carly S Lundgreen  2 , Maria Vassilaki  2 , Walter K Kremers  2 , David S Knopman  3 , Ronald C Petersen  3 , Daniel J Berry  4 , David G Lewallen  4 , Paul J Jannetto  1 , Melissa E Murray  1 , R Ross Reichard  1 , Hilal Maradit Kremers  5   6
Affiliations

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

Blake A Ebner et al. Acta Neuropathol. .

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.

Keywords: Alzheimer disease pathology; Arthroplasty; Autopsy; Chromium; Cobalt; Titanium.

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Conflict of interest statement

Declarations. Conflict of interest: Dr Vassilaki reported receiving research funding from F. Hoffmann-La Roche Ltd and Biogen in the past and consults for F. Hoffmann-La Roche Ltd., receiving research funding from NIH and has equity ownership in Abbott Laboratories, Johnson and Johnson, Medtronic and Amgen. Dr Kremers reported receiving research support from the National Institutes of Health. Dr Knopman serves on a Data Safety Monitoring Board for the DIAN study, is an investigator in clinical trials sponsored by Lilly Pharmaceuticals, Biogen and the Alzheimers Treatment and Research Institute at USC, and reported receiving research support from the National Institutes of Health. Dr Petersen is a consultant for Roche, Inc., Biogen, Inc., Merck, Inc., Eisai, Inc., Genentech, Inc. and Nestle, Inc., reported receiving publishing royalties from Mild Cognitive Impairment (Oxford University Press, 2003), UpToDate and reported receiving research support from the National Institutes of Health. Dr Berry reported receiving royalties, consulting fees and/or stock options from Elsevier, Wolters Kluwer, Journal of Bone and Joint Arthroplasty, Depuy, Bodycad, has leadership roles in Orthopaedic Research and Education Foundation, International Hip Society, Knee Society, International Society of Arthroplasty Registries, Current Concepts in Joint Replacement, Journal of Bone and Joint Surgery, reported receiving research support from the National Institutes of Health. Dr Lewallen reported receiving royalties, consulting fees and/or stock options from Zimmer Biomet, Ketai Medical Devices, Accuitive, reported receiving research support from the National Institutes of Health. Dr Maradit Kremers reported receiving research support from the National Institutes of Health.

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