A Metallomic Approach to Assess Associations of Plasma Metal Levels with Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: An Exploratory Study

Abstract

Alzheimer’s disease (AD) involves the abnormal activity of transition metals and metal ion dyshomeostasis; however, the potential of trace metal biomarkers in predicting cognitive decline has not been evaluated. This study aimed to assess the potential of 36 trace elements in predicting cognitive decline in patients with amnestic mild cognitive impairment (aMCI) or AD. Participants (9 controls, 23 aMCI due to AD, and 8 AD dementia) underwent comprehensive cognitive tests, including the Mini-Mental State Examination (MMSE) and trace metal analysis. The correlations between the plasma trace element levels and annual MMSE changes during follow-up were analyzed. We found that an increase in disease severity was linked to lower plasma levels of boron (B), bismuth (Bi), thorium (Th), and uranium (U) (adjusted p < 0.05). Higher baseline calcium levels (r = 0.50, p = 0.026) were associated with less annual cognitive decline; those of B (r = −0.70, p = 0.001), zirconium (r = −0.58, p = 0.007), and Th (r = −0.52, p = 0.020) with rapid annual cognitive decline in the aMCI group; and those of manganese (r = −0.91, p = 0.035) with rapid annual cognitive decline in the AD group. Overall, our exploratory study suggests that plasma metal levels have great potential as in vivo biomarkers for aMCI and AD. Larger sample studies are necessary to confirm these results.

Natural antioxidants that act against Alzheimer’s disease through modulation of the NRF2 pathway: a focus on their molecular mechanisms of action

“…Copper, zinc and iron ions are very important for the biological functions of metalloproteins as well as for neuronal processes. In the case of neurodegenerative diseases, such as AD, there is a disruption of metal ion homeostasis in the brain ( 60 ). Zinc and copper cations bind to the hydrophilic N-termini of Aβ peptides and undergo continuous redox reactions, promoting the generation of ROS and causing a vicious cycle of increased oxidation and ROS production, which results in the accumulation of toxic Aβ peptides that cannot exit the synapse.…”