Plasma levels of HDL and carotenoids are lower in dementia patients with vascular comorbidities

Irundika H.K. Dias, Maria Cristina Polidori, Li Li, Daniela Weber, Wilhelm Stahl, Gereon Nelles, Tilman Grune, Helen R. Griffiths

Research output: Contribution to journalArticle

Abstract

Elevated serum cholesterol concentrations in mid-life increase risk for Alzheimer's disease (AD) in later life. However, lower concentrations of cholesterol-carrying high density lipoprotein (HDL) and its principal apolipoprotein A1 (ApoA1) correlate with increased risk for AD. As HDL transports oxocarotenoids, which are scavengers of peroxynitrite, we have investigated the hypothesis that lower HDL and oxocarotenoid concentrations during AD may render HDL susceptible to nitration and oxidation and in turn reduce the efficiency of reverse cholesterol transport (RCT) from lipid-laden cells. Fasting blood samples were obtained from subjects with 1) AD without cardiovascular comorbidities and risk factors (AD); 2) AD with cardiovascular comorbidities and risk factors (AD Plus); 3) normal cognitive function; for carotenoid determination by HPLC, analysis of HDL nitration and oxidation by ELISA, and 3H-cholesterol export to isolated HDL. HDL concentration in the plasma from AD Plus patients was significantly lower compared to AD or control subject HDL levels. Similarly, lutein, lycopene, and zeaxanthin concentrations were significantly lower in AD Plus patients compared to those in control subjects or AD patients, and oxocarotenoid concentrations correlated with Mini-Mental State Examination scores. At equivalent concentrations of ApoA1, HDL isolated from all subjects irrespective of diagnosis was equally effective at mediating RCT. HDL concentration is lower in AD Plus patients' plasma and thus capacity for RCT is compromised. In contrast, HDL from patients with AD-only was not different in concentration, modifications, or function from HDL of healthy age-matched donors. The relative importance of elevating HDL alone compared with elevating carotenoids alone or elevating both to reduce risk for dementia should be investigated in patients with early signs of dementia.

LanguageEnglish
Pages399-408
Number of pages10
JournalJournal of Alzheimer's disease
Volume40
Issue number2
Early online date21 Jan 2014
DOIs
Publication statusPublished - Jan 2014

Fingerprint

Carotenoids
HDL Lipoproteins
Blood Vessels
Dementia
Comorbidity
Alzheimer Disease
Cholesterol
Lutein
Peroxynitrous Acid
Apolipoproteins
Apolipoprotein A-I
Hypercholesterolemia
Cognition
HDL Cholesterol
Fasting
Enzyme-Linked Immunosorbent Assay
High Pressure Liquid Chromatography
Tissue Donors
Lipids

Bibliographical note

This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License.

Keywords

  • 3-nitrotyrosine
  • aging
  • alzheimer's disease
  • free radical scavenger
  • protein carbonyl formation
  • protein oxidation

Cite this

Dias, Irundika H.K. ; Polidori, Maria Cristina ; Li, Li ; Weber, Daniela ; Stahl, Wilhelm ; Nelles, Gereon ; Grune, Tilman ; Griffiths, Helen R. / Plasma levels of HDL and carotenoids are lower in dementia patients with vascular comorbidities. In: Journal of Alzheimer's disease. 2014 ; Vol. 40, No. 2. pp. 399-408.
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abstract = "Elevated serum cholesterol concentrations in mid-life increase risk for Alzheimer's disease (AD) in later life. However, lower concentrations of cholesterol-carrying high density lipoprotein (HDL) and its principal apolipoprotein A1 (ApoA1) correlate with increased risk for AD. As HDL transports oxocarotenoids, which are scavengers of peroxynitrite, we have investigated the hypothesis that lower HDL and oxocarotenoid concentrations during AD may render HDL susceptible to nitration and oxidation and in turn reduce the efficiency of reverse cholesterol transport (RCT) from lipid-laden cells. Fasting blood samples were obtained from subjects with 1) AD without cardiovascular comorbidities and risk factors (AD); 2) AD with cardiovascular comorbidities and risk factors (AD Plus); 3) normal cognitive function; for carotenoid determination by HPLC, analysis of HDL nitration and oxidation by ELISA, and 3H-cholesterol export to isolated HDL. HDL concentration in the plasma from AD Plus patients was significantly lower compared to AD or control subject HDL levels. Similarly, lutein, lycopene, and zeaxanthin concentrations were significantly lower in AD Plus patients compared to those in control subjects or AD patients, and oxocarotenoid concentrations correlated with Mini-Mental State Examination scores. At equivalent concentrations of ApoA1, HDL isolated from all subjects irrespective of diagnosis was equally effective at mediating RCT. HDL concentration is lower in AD Plus patients' plasma and thus capacity for RCT is compromised. In contrast, HDL from patients with AD-only was not different in concentration, modifications, or function from HDL of healthy age-matched donors. The relative importance of elevating HDL alone compared with elevating carotenoids alone or elevating both to reduce risk for dementia should be investigated in patients with early signs of dementia.",
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Dias, IHK, Polidori, MC, Li, L, Weber, D, Stahl, W, Nelles, G, Grune, T & Griffiths, HR 2014, 'Plasma levels of HDL and carotenoids are lower in dementia patients with vascular comorbidities' Journal of Alzheimer's disease, vol. 40, no. 2, pp. 399-408. https://doi.org/10.3233/JAD-131964

Plasma levels of HDL and carotenoids are lower in dementia patients with vascular comorbidities. / Dias, Irundika H.K.; Polidori, Maria Cristina; Li, Li; Weber, Daniela; Stahl, Wilhelm; Nelles, Gereon; Grune, Tilman; Griffiths, Helen R.

In: Journal of Alzheimer's disease, Vol. 40, No. 2, 01.2014, p. 399-408.

Research output: Contribution to journalArticle

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T1 - Plasma levels of HDL and carotenoids are lower in dementia patients with vascular comorbidities

AU - Dias, Irundika H.K.

AU - Polidori, Maria Cristina

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AU - Weber, Daniela

AU - Stahl, Wilhelm

AU - Nelles, Gereon

AU - Grune, Tilman

AU - Griffiths, Helen R.

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N2 - Elevated serum cholesterol concentrations in mid-life increase risk for Alzheimer's disease (AD) in later life. However, lower concentrations of cholesterol-carrying high density lipoprotein (HDL) and its principal apolipoprotein A1 (ApoA1) correlate with increased risk for AD. As HDL transports oxocarotenoids, which are scavengers of peroxynitrite, we have investigated the hypothesis that lower HDL and oxocarotenoid concentrations during AD may render HDL susceptible to nitration and oxidation and in turn reduce the efficiency of reverse cholesterol transport (RCT) from lipid-laden cells. Fasting blood samples were obtained from subjects with 1) AD without cardiovascular comorbidities and risk factors (AD); 2) AD with cardiovascular comorbidities and risk factors (AD Plus); 3) normal cognitive function; for carotenoid determination by HPLC, analysis of HDL nitration and oxidation by ELISA, and 3H-cholesterol export to isolated HDL. HDL concentration in the plasma from AD Plus patients was significantly lower compared to AD or control subject HDL levels. Similarly, lutein, lycopene, and zeaxanthin concentrations were significantly lower in AD Plus patients compared to those in control subjects or AD patients, and oxocarotenoid concentrations correlated with Mini-Mental State Examination scores. At equivalent concentrations of ApoA1, HDL isolated from all subjects irrespective of diagnosis was equally effective at mediating RCT. HDL concentration is lower in AD Plus patients' plasma and thus capacity for RCT is compromised. In contrast, HDL from patients with AD-only was not different in concentration, modifications, or function from HDL of healthy age-matched donors. The relative importance of elevating HDL alone compared with elevating carotenoids alone or elevating both to reduce risk for dementia should be investigated in patients with early signs of dementia.

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