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Cerebrospinal fluid Alzheimer's biomarker profiles in CNS infections

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Abstract

The cerebrospinal fluid (CSF) biomarker profile in Alzheimer's disease (AD) is characterized by decreased beta amyloid (Aβ1-42), increased total and hyperphosphorylated tau (t-tau and p-tau, respectively), which is a useful diagnostic tool and gives insight in the pathogenesis of AD. It is of importance to study how these biomarkers react in other CNS diseases; therefore, we decided to analyse amyloid and tau biomarkers in different CNS infections. We also included analysis of soluble amyloid precursor proteins (sAPPα and -β). CSF Aβ1-42, sAPPα and -β, t-tau and p-tau were analysed in bacterial meningitis (n = 12), Lyme neuroborreliosis (n = 13), herpes simplex virus type 1 (HSV-1) encephalitis (n = 10), HIV-associated dementia (HAD) (n = 21), AD (n = 21) and healthy controls (n = 42). Concurrent with AD, Aβ1-42 was decreased in all groups except neuroborreliosis compared to controls. HSV-1 encephalitis, bacterial meningitis and HAD showed lower concentrations of sAPPα and -β compared to AD. T-tau was increased in AD and HSV-1 encephalitis compared to all other groups. P-tau was higher in AD and HSV-1 encephalitis compared to bacterial meningitis, HAD and control. Decreased CSF Aβ1-42, sAPPα and -β in various CNS infections imply an effect of neuroinflammation on amyloid metabolism which is similar in regard to AD concerning Aβ1-42, but differs concerning sAPPα and -β. These results clearly indicate different pathologic pathways in AD and infectious CNS disease and may provide help in the differential biomarker diagnostics. Increased p-tau in HSV-1 encephalitis probably reflect acute neuronal damage and necrosis.

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Acknowledgments

The study was supported by Sahlgrenska Academy at the University of Gothenburg (ALFGBG-11067), Swedish Research Council (project 2007–7092), Göteborg Medical Society.

Conflicts of interest

Dr. Krut declare that he has no conflicts of interest. Dr. Zetterberg declare that he has no conflicts of interest. Dr. Blennow declare that he has no conflicts of interest. Dr. Cinque declare that she has no conflicts of interest. Dr. Hagberg declare that he has no conflicts of interest. Dr. Price has received research grant support from Merck and Company for an investigator-initiated study and a speaking honorarium from Abbott Laboratories. Dr. Studahl received research funding from Sanofi Pasteur MSD. Dr. Gisslén declare that he has no conflicts of interest.

Ethical standard

All human studies must state that they have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

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Authors and Affiliations

  1. Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden

    Jan Jessen Krut, Lars Hagberg, Marie Studahl & Magnus Gisslén

  2. Department of Clinical Neuroscience, University of Gothenburg, Gothenburg, Sweden

    Henrik Zetterberg & Kaj Blennow

  3. Clinic of Infectious Diseases, San Raffaele Hospital, Milan, Italy

    Paola Cinque

  4. Department of Neurology, San Francisco General Hospital, University of California, San Francisco, CA, USA

    Richard W. Price

  5. Department of Infectious Diseases, Sahlgrenska University Hospital, Smörslottsgatan 1, 41678, Göteborg, Sweden

    Jan Jessen Krut

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  1. Jan Jessen Krut
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Correspondence to Jan Jessen Krut.

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Krut, J.J., Zetterberg, H., Blennow, K. et al. Cerebrospinal fluid Alzheimer's biomarker profiles in CNS infections. J Neurol 260, 620–626 (2013). https://doi.org/10.1007/s00415-012-6688-y

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  • DOI: https://doi.org/10.1007/s00415-012-6688-y

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