Post-mortem human Alzheimer´s brain metallome depends on Braak stages and brain regions

Abstract Limited studies have evaluated the influence of redox-related metals on the Alzheimer´s brain. We determined 15 metals in 241 human brain samples obtained from five biobanks. We examined the levels of metals in the frontal cortex (CTX) and the basal ganglia (BG) of Alzheimer´s brains of different stages, ranging from Braak stages I and II to Braak stages V and VI. Imbalances measured metals in the Alzheimer´s brain metallome of different Braak stages and different regions compared to controls, and associations between metals and Braak stages were estimated by the Kruskal-Wallis Test and Spearman correlations, respectively. We observed higher levels of Mn, Cu, Mo, and Se and lower levels of Co in Alzheimer´s CTX compared to the controls, and higher levels of V and Cr and lower levels of Co in BG. Metals may differ in Braak stages across different human brain regions. Although the etiology of Alzheimer´s disease (AD) remains unclear, the amyloid cascade hypothesis is the most widely accepted. Thus, the accumulation of amyloid beta (Aβ42) in the brain would be the primary event in the cascade that leads to p-tau hyperphosphorylation, neurofibrillary tangle (NFT) formation, synaptic dysfunction, and neuronal death.