engleski

Dynamics of blood and cerebrospinal fluid biomarkers of Alzheimer's disease

Introduction: Dyshomeostasis of essential metals has been proposed to be directly related to Alzheimer’s disease (AD) pathological changes. Materials and methods: We analyzed cerebrospinal fluid (CSF) and venous blood samples of 124 AD, 50 mild cognitive impairment (MCI) subjects, and 19 healthy controls. Eleven AD biomarkers were measured in CSF by using the enzyme-linked immunosorbent assay: Aβ42, VILIP-1, t-tau, p- tau181, p-tau231, p-tau199, NF-L, S100B, YKL-40, PAPP-A, and albumin. Inductively coupled plasma mass spectroscopy was used for the measurement of CSF and plasma levels of the following elements: As, B, Ca, Cd, Co, Cu, Fe, Hg, Li, Mg, Mn, Mo, Na, Ni, P, Pb, S, Se, Sr, Tl and Zn, and CSF levels of Al, Ba, and K. Correlation and linear regression were used for testing of the association between protein biomarkers and elements measured. The principal component analysis was used to reduce the dimensionality. Results: The elements that correlated with the high number of AD biomarkers in CSF were As, Hg, Zn, Cu, Fe, S, K, Se, Co, Mn, Ni, Na, Mg, Tl, and Li. Factor analysis of CSF included 23 parameters that explained around three-quarters of the total variance, whereas factor analysis of elements in plasma included 21 parameters, which explained around two-thirds of the total variance. Using redescription mining, we found six potentially interesting cooccurrences between AD protein biomarkers and elements analyzed. Conclusions: Using three different methods of data analysis on a relatively large data set we confirmed dyshomeostasis of essential elements in CSF and plasma in AD and MCI subjects.

Alzheimer’s disease ; heavy metals ; essential metals ; cerebrospinal fluid ; biomarker ; arsenic ; mercury ; cadmium ; iron ; zinc ; calcium

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