Evidence that levels of nine essential metals in post-mortem human-Alzheimer's-brain and ex vivo rat-brain tissues are unaffected by differences in post-mortem delay, age, disease staging, and brain bank location

Abstract

Studies of neurodegenerative conditions such as Alzheimer's disease (AD) using post mortem brain tissues have uncovered several perturbations in metals such as copper, iron, and zinc. However, studies of the effects of key, potentially confounding variables on these tissues are currently lacking. Moreover, human-brain tissues have limited availability, further enhancing the difficulty of matching potentially-significant variables including age, sex-matching, post-mortem delay (PMD), and neuropathological stage. This study aimed to investigate the effects of such factors and how they might influence metal concentrations in post-mortem brains. Cingulate gyrus from AD cases and matched controls was obtained from two brain banks, based in Auckland, New Zealand and Manchester, UK. Inductively-coupled plasma mass spectrometry (ICP-MS) was employed to measure levels of nine essential metals in brain tissues, and compared concentrations between cases and controls, and between cohorts, to analyse effects of age, sex, Braak stage, brain weight, and PMD. The same methods were used to investigate the effects of PMD under more controlled conditions using ex vivo healthy adult rat-brain tissue. Metal concentrations in human brain were found to be unmodified by differences in age, sex-matching, Braak stage, brain weight, and PMD between cohorts. Some metals were, however, found to vary significantly across different regions in rat brains. These results indicate that investigations of metal homeostasis in AD and other neurodegenerative conditions can be reliably performed using brain tissues without confounding by varying PMD, age, sex-matching, brain weight, and Braak stage. However, regions of study should be selected carefully.