Eur Arch Psychiatry Clin Neurosci (2005) 255 : 269–278 DOI 10.1007/s00406-004-0558-2 ■ Abstract Involvement of the interleukin-6 receptor complex (IL-6RC) in neuroregulatory and immunologi- cal processes of the brain and particularly in Alzheimer’s disease (AD) has been hypothesized. The functionally active IL-6RC consists of the cytokine IL-6, which acts through the ligand binding IL-6R and the signal trans- ducing gp130. Using a new immunocytochemical proto- col on rapid autopsy cryostat brain sections we studied the expression of the IL-6RC in Braak IV-V staged AD pa- tients compared to normal age-matched controls (HC) across five different cortical regions. Inter-rater reliabil- ity of the method was high. The “baseline” expression in normal human brain was determined for IL-6, IL-6R and gp130 in all cortical regions. In normal tissue IL-6 ex- pression was lower in parietal cortex. Higher IL-6R ex- pression was shown in frontal,occipital and parietal cor- tex,lower expression in temporal cortex and cerebellum. In AD IL-6 expression levels were generally increased in parietal cortex and decreased in occipital cortex com- pared to controls. IL-6R expression levels were strongly increased in AD frontal and occipital cortex and de- creased in temporal cortex and cerebellum. Our findings indicate an altered cortical immunoreactivity pattern of the functional IL-6RC in AD supporting the hypothesis of a disease-related role of IL-6 in AD pathophysiology. ■ Key words Alzheimer’s disease · interleukin-6 receptor · cytokine receptors · gp130 · immunocytochemistry · rapid autopsy Introduction Interleukin-6 (IL-6) is a multifunctional cytokine that modulates multiple effects on the immune, hematopoi- etic and the central nervous systems (CNS) (Heinrich et al. 1990, 1998; Hirano et al. 1997;Van Snick et al. 1990). IL-6 has been reported to serve as an important media- tor of neuroregulatory and inflammatory processes in the CNS (Kishimoto et al. 1992; Vandenabeele et al. 1991). In particular, IL-6 may play a role in controlling neuroimmune responses and neuronal protection and growth (Campbell et al. 1993; Gruol et al. 1997; Hama et al. 1989, 1991), and may serve as an early marker of tis- sue damage in the brain (Gruol et al. 1997). ORIGINAL PAPER Harald Hampel · Andreas Haslinger · Michael Scheloske · Frank Padberg · Petra Fischer · Josef Unger · Stefan Johannes Teipel · Michaela Neumann · Carlyn Rosenberg · Rusti Oshida · Christine Hulette · Dieter Pongratz · Michael Ewers · H.A. Kretzschmar · Hans-Jürgen Möller Pattern of interleukin-6 receptor complex immunoreactivity between cortical regions of rapid autopsy normal and Alzheimer’s disease brain Received: 23 June 2004 / Accepted: 27 September 2004 / Published online: 26 November 2004 EAPCN 558 H. Hampel, M. D. () · A. Haslinger · M. Scheloske · F. Padberg · S. J. Teipel · M. Ewers · H.-J. Möller Alzheimer Memorial Centre Geriatric Psychiatric Branch Dementia Research Section Dept. of Psychiatry Ludwig-Maximilian University Nussbaumstr. 7 80336 Munich, Germany Tel.: +49-89/5160-5877 Fax: +49-89/5160-5856 E-Mail: hampel@psy.med.uni-muenchen.de P. Fischer · D. Pongratz Friedrich-Baur-Institute Ludwig-Maximilian University Munich, Germany J. Unger Dept. of Anatomy Ludwig-Maximilian University Munich, Germany M. Neumann · H. A. Kretzschmar Dept. of Neuropathology Ludwig-Maximilian University Munich, Germany C. Rosenberg · C. Hulette Kathleen Price Bryan Brain Bank Bryan Alzheimer’s Disease Research Center Duke University Medical Center Durham (NC), USA R. Oshida Institute for Brain Aging and Dementia University of California Brain Aging Neuropathology Core Patient Summary Irvine (CA), USA Preliminary parts of this work were presented in abstract form at the 28 th Annual Meeting of the Society of Neuroscience, Los Angeles, CA, 1998, at the 29 th Annual Meeting of the Society of Neuroscience, Miami, FL, 1999, at the Neuroinflammation Conference, Washington, DC, 2000 and at the 30 th Annual Meeting of the Society of Neuro- science, New Orleans, LA, 2000.