Trace Elements in Medicine (Moscow)
2016, 17(4): 3-10
TOPICAL PAPER

METAL-LIGAND HOMEOSTASIS IN ETIOPATHOGENESIS OF ALZHEIMER'S DISEASE (REVIEW)

L.L. Klimenko1, A.V. Skalny2, A.A. Turna3, А.I. Deev1, M.N. Budanova1, I.S. Baskakov1, Е.А. Nikonorova 2

1 N.N. Semenov Institute of Chemical Physics at Russian Academy of Sciences, Kosygina str. 4, Moscow, 117334, Russia
2 ANO Centre for Biotic Medicine, Zemlyanoi val 46, Moscow 105064, Russia
3 Institute of Professional Development at FMBA of Russia, Volokolamskoe shosse 91, Moscow, 125371, Russia

DOI: 10.19112/2413-6174-2016-17-4-3-10 

ABSTRACT. Alzheimer's disease (AD) is characterized by impaired synaptic transmission, neuronal loss, the deposition of the protein beta-amyloid (β Ap) in the brain structures responsible for memory and consciousness. Reduced glucose consumption, glutamate excitotoxicity, lactic acidosis and oxidative stress, decrease in ATP production – all these biochemical reactions lower energy metabolism in the brain. Increased level of oxidative stress in AD brain is associated with higher brain content of iron (Fe) and copper (Cu), which stimulate the formation of free radicals. High biological activity of trace elements is due to their participating in the molecules of metalloenzymatic systems as structural units. Zinc is a metal, which is crucial for the formation of synaptic transmission, it is involved in the etiopathogenesis of AD. Copper is a cofactor for the antioxidant enzyme superoxide dismutase. Disturbance of copper homeostasis leads to AD. Copper and manganese concentrations in AD patients were significantly higher than in the control group. Selenium is a trace element-antioxidant, an important regulator of brain functions. At the oxidative stress that accompanies the development of AD, Se depletion followed by reduced activity of Se-dependent enzymes is an important pathogenetic factor. Physiological selenium intake is acknowledged as a protective factor against neurodegeneration. At AD, a change of magnesium transmembrane transport occurs. Cytosolic magnesium deficiency in neurons is the earliest marker of nerve cells apoptosis at AD. The whole complex of biochemical changes occurring in the brain at Alzheimer's disease leads to inhibition of its energy metabolism that correlates with early cognitive disadvantage. Local cerebral blood flow in the association areas in AD patients is decreased; lactate production is increased in connection with the reduction of aerobic oxidation and an intensification of glycolysis. Functional imaging techniques play an important role in the study of brain energy metabolism by monitoring changes in blood flow and energy metabolism at AD. The use of representative biomarkers, such as indicators of metal-ligand homeostasis and energy metabolism of the brain allows us to proactively assess the state of the brain and prevent the development of neurodegenerative diseases, long before the first clinical signs.

KEYWORDS: Alzheimer's disease, biomarkers, β-amyloid, metal-ligand homeostasis, macroelements, trace elements.