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Human Cytokine Response to ex vivo Amyloid-β Stimulation is Mediated by Genetic Factors

Published online by Cambridge University Press:  21 February 2012

Danielle Posthuma
Affiliation:
Department of Biological Psychology, Vrije Universiteit Amsterdam, the Netherlands. danielle@psy.vu.nl
Ingrid Meulenbelt
Affiliation:
Department of Medical Statistics, Leiden University Medical Center, the Netherlands.
Anton J. M. de Craen
Affiliation:
Department of General Internal Medicine, Leiden University Medical Center, the Netherlands.
Eco J. C. de Geus
Affiliation:
Department of Biological Psychology, Vrije Universiteit Amsterdam, the Netherlands.
P. Eline Slagboom
Affiliation:
Department of Medical Statistics, Leiden University Medical Center, the Netherlands.
Dorret I. Boomsma
Affiliation:
Department of Biological Psychology, Vrije Universiteit Amsterdam, the Netherlands.
Rudi G. J. Westendorp
Affiliation:
Department of General Internal Medicine, Leiden University Medical Center, the Netherlands.
Corresponding
E-mail address:

Abstract

Through its ability to induce the enhanced release and production of cytokines, amyloid-β is responsible for the chronic inflammatory response that contributes to Alzheimer's disease (AD). Determining whether the response of monocytes to amyloid-β stimulation is under genetic control may help understand the basis of why some people are more prone to develop neuronal degeneration than others. In the current study we investigated the heritability of the cytokine (IL-10, IL-6, IL-1β, IL-1ra, TNF-[.alpha]) production capacity upon ex vivo stimulation with amyloid-β in whole blood samples of 222 twins and 85 singleton siblings from 139 extended twin families. It was found that individual differences in amyloid-β-induced cytokine production capacity are to a large extent of genetic origin, with heritability estimates ranging from 55% (IL-1β) to 68% (IL-6). We conclude that genes influencing amyloid-β-induced cytokine response may provide clues to the progression of AD pathology.

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Copyright © Cambridge University Press 2005
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