Screening of innate immune receptors in neurodegenerative diseases: A similar pattern

Letiembre, Maryse; Liu, Yang; Walter, Silke; Hao, Wenlin; Pfander, Tatjana; Wrede, Arne; Schulz-Schaeffer, Walter; Fassbender, Klaus

doi:10.1016/j.neurobiolaging.2007.08.018

« Previous Next »Neurobiology of Aging
Volume 30, Issue 5 , Pages 759-768, May 2009

Screening of innate immune receptors in neurodegenerative diseases: A similar pattern

Maryse Letiembre
- University of the Saarland, Department of Neurology, Kirrberger Strasse, 66421 Homburg/Saar, Germany
- Corresponding author. Tel.: +49 6841 16 47 913; fax: +49 6841 16 47 801.
Yang Liu
- University of the Saarland, Department of Neurology, Kirrberger Strasse, 66421 Homburg/Saar, Germany
Silke Walter
- University of the Saarland, Department of Neurology, Kirrberger Strasse, 66421 Homburg/Saar, Germany
Wenlin Hao
- University of the Saarland, Department of Neurology, Kirrberger Strasse, 66421 Homburg/Saar, Germany
Tatjana Pfander
- University of Göttingen, Department of Neuropathology, Robert-Koch Strasse 40, 37075 Göttingen, Germany
Arne Wrede
- University of Göttingen, Department of Neuropathology, Robert-Koch Strasse 40, 37075 Göttingen, Germany
Walter Schulz-Schaeffer
- University of Göttingen, Department of Neuropathology, Robert-Koch Strasse 40, 37075 Göttingen, Germany
- These authors contributed equally to this work.
Klaus Fassbender
- University of the Saarland, Department of Neurology, Kirrberger Strasse, 66421 Homburg/Saar, Germany
- These authors contributed equally to this work.
- Corresponding author. Tel.: +49 6841 16 24 103; fax: +49 6841 16 24 137.

Received 10 June 2007; received in revised form 10 August 2007; accepted 14 August 2007. published online 01 October 2007.

Abstract

In Alzheimer's disease (AD), Parkinson's disease (PD), dementia with Lewy bodies (DLB) and amyotrophic lateral sclerosis (ALS), neuroinflammatory responses are considered to contribute to neuronal injury. Recently, the innate immune receptors, toll-like receptors (TLRs) and the LPS receptor (CD14) have been related to neurodegeneration. In this study, we systematically assessed the expression of most TLRs and CD14 in AD, PD/DLB and ALS using murine models of these diseases and human post-mortem brain tissues. A common upregulation of TLR2 and CD14 was found in all three animal models. While these two receptors could also be detected in AD patient tissues, they were absent from DLB and ALS tissues. This uniform pattern of innate immune response in animal models of neurodegenerative diseases clearly indicates that this response is part of a non-specific neuroinflammatory effector phase rather than a disease-specific event. The less dynamic disease progression in humans and the location (extracellular versus intracellular) of the aggregated proteins deposits might explain the divergent results seen between animal models and human tissues.

Keywords: Innate immunity, Toll-like receptors, CD14, Brain aging, Neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, Lewy bodies dementia, Amyotrophic lateral sclerosis