Oxidative LDL modification is increased in vascular dementia and is inversely associated with cognitive performance

Abstract

It is not known whether the association between increased plasma homocysteine (Hcy) associated with LDL modification and propensity for LDL uptake by macrophages in cardiovascular disease patients holds true in vascular dementia (VaD). Plasma from 83 subjects diagnosed with Alzheimer's disease (AD), VaD, mild cognitive impairment (MCI) and from controls was analysed to examine (1) whether LDL isolated from the plasma of VaD is biochemically and functionally distinct from that isolated from AD, MCI or controls; and (2) whether such biomarkers of LDL phenotype are related to plasma folate levels, Hcy levels and/or to disease severity. Folate and vitamin B6 levels were significantly lower in VaD subjects than in controls. VaD-LDL showed increased protein carbonyl content (p < 0.05) and was more susceptible to scavenging by macrophages (p < 0.05) than AD- or control-LDL. Patients from the VaD cohort were more prevalent in the lowest tertile for HDL:LDL and the upper tertile for LDL oxidation; the combined parameters of HDL cholesterol, LDL oxidation and scavenging by macrophages show 87% sensitivity towards VaD detection. The association between folate deficiency, LDL modification and dysfunction in VaD but not in AD may provide a novel biomarker assessment to discriminate between the diseases.

Keywords::

• Alzheimer's dementia
• vascular dementia
• mild cognitive impairment
• LDL oxidation
• homocysteine
• folate
• inflammation

Declaration of interest:

H.R.G. gratefully acknowledges financial support from the Alzheimer's Research Trust and the help of the School of Biochemistry and Immunology, Trinity College, Dublin, Ireland, for folate and vitamin B12 analyses. L.L. acknowledges financial support for the PhD studentship from the ORSAS and a travelling fellowship from DAAD. Sample analysis for transcobalamin was kindly undertaken for H.R.G. by Alexis Shield.

H.S. is a Fellow of the National Foundation for Cancer Research (NFCR), Bethesda, MD. M.C.P. is a Fellow of the Forschungskolleg Geriatrie from the Robert Bosch Foundation, Stuttgart, Germany. The authors report no conflicts of interest.

The authors alone are responsible for the content and writing of the paper.

This paper was first published online on Early Online on 2 December 2009.