Characterization of metal profiles in serum during the progression of Alzheimer's disease

Abstract

Metal dyshomeostasis is closely related to Alzheimer's disease, so the characterization of the metal profiles in these patients is of special interest for studying associated neurodegenerative processes and to discover potential markers of disease. An analytical approach, based on non-denaturing precipitation of proteins, has been optimized for the fractionation of high molecular mass (HMM) and low molecular mass (LMM) metal-species from serum, which were subjected to multielemental analysis by inductively coupled plasma mass spectrometry (ICP-MS). This methodology was applied to healthy controls, Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients in order to study the progression of dementia. Thus, it was found that some metals, such as iron, copper, zinc and aluminium, suffer progressive changes along the advance of neurodegeneration, suggesting that these imbalances could be related to the decline of cognitive functions. On the other hand, elements such as manganese, lithium or vanadium allow discriminating between controls and diseased subjects, both AD and MCI, but no differences were found between these two clinical stages, so they could be considered as precursors in the early development of neurodegenerative failures. In addition, it should be noted the important role that low molecular mass fractions of iron, copper, aluminium and cobalt appear to play in pathogenesis of Alzheimer. Finally, correlation analysis indicated that these metal abnormalities can be interrelated, participating in common processes such as oxidative stress, altered homeostasis and uptake into brain, as well as impaired glucose metabolism.