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Cerebrospinal fluid levels of complement proteins C3, C4 and CR1 in Alzheimer’s disease

  • Dementias - Original Article
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Abstract

Alzheimer’s disease (AD) is strongly associated with loss of synapses. The complement system has been shown to be involved in synaptic elimination. Several studies point to an association between AD and the complement system. The purpose of this study was to examine the association of cerebrospinal fluid (CSF) levels of complement components 3 and 4 (C3 and C4, respectively), and complement receptor 1 (CR1) with AD in 43 patients with AD plus dementia, 42 patients with mild cognitive impairment (MCI) who progressed to AD during follow-up (MCI-AD), 42 patients with stable MCI and 44 controls. Complement levels were also applied in a multivariate model to determine if they provided any added value to the core AD biomarkers Aβ42, T-tau and P-tau. We found elevated CSF levels of C3 and C4 in AD compared with MCI without progression to AD, and elevated CSF levels of CR1 in MCI-AD and AD when these groups were merged. These results provide support for aberrant complement regulation as a part in the AD process, but the changes are not diagnostically useful.

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Acknowledgments

The authors thank Åsa Källén, Monica Christiansson, Dzemila Secic and Sara Hullberg for skillful technical assistance, and Doctor Rochelle Ackerley for helpful comments on the manuscript. This study was supported by grants from the Sahlgrenska Academy, the Swedish Research Council (K2010-63P-21562-01-4, K2011-61X-20401-05-6, K2011-62X-21857-01-6, K2011-62X-21710-01-1, K2010-62X-12600-13-3), the Söderberg Foundation, Alzheimer’s Association, Gun and Bertil Stohne’s Foundation, Stiftelsen för Gamla Tjänarinnor, The Swedish Alzheimer Foundation, ALF funding for medical training and research and Swedish State Support for Clinical Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 405 30, Gothenburg, Sweden

    Jonny Daborg & Eric Hanse

  2. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden

    Ulf Andreasson, Ronald Lautner, Kaj Blennow & Henrik Zetterberg

  3. UCL Institute of Neurology, London, WC1N 3BG, UK

    Henrik Zetterberg

  4. Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

    Marcela Pekna

  5. Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden

    Lennart Minthon & Oskar Hansson

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  1. Jonny Daborg
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  2. Ulf Andreasson
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Correspondence to Jonny Daborg.

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Daborg, J., Andreasson, U., Pekna, M. et al. Cerebrospinal fluid levels of complement proteins C3, C4 and CR1 in Alzheimer’s disease. J Neural Transm 119, 789–797 (2012). https://doi.org/10.1007/s00702-012-0797-8

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