Detection of interleukin-6 and alpha 2-macroglobulin immunoreactivity in cortex and hippocampus of Alzheimer's disease patients.
We examined brains from Alzheimer's disease (AD) patients by immunohistochemistry for the presence of protease inhibitors. Immunoreactivity for alpha 2-macroglobulin (alpha 2-M), the most potent of the known human protease inhibitors, was found in a subgroup of cortical and hippocampal AD senile plaques. In addition, large hippocampal neurons in AD brains displayed intracellular alpha 2-M immunoreactivity which was consistently stronger than in normal aged brains. In cultured human cells of neurogenic origin (SH-SY5Y neuroblastoma cells), alpha 2-M synthesis could be strongly induced by the inflammatory cytokine interleukin-6 (IL-6) indicating that human alpha 2-M behaves as an acute-phase protein in the nervous system. Therefore, we also examined AD brains for the presence of IL-6 and found strong immunostaining in and around a subgroup of senile plaques as well as around large cortical neurons. Only very few senile plaques also stained for C-reactive protein, an acute phase protein known to be inducible by IL-6. We propose that the presence of IL-6 and alpha 2-M immunoreactivity in AD brains is functionally linked and that a sequence of immunological events is part of the pathology of AD.
Abteilung Neuropathologie, Universität Freiburg, Germany.
S
S
Strauss
J
J
Bauer
U
U
Ganter
U
U
Jonas
M
M
Berger
B
B
Volk
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D002540:Cerebral Cortex / Q000737:chemistry*; D006624:Hippocampus / Q000737:chemistry*; D006801:Humans; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000032:analysis*; D015531:Radioimmunoprecipitation Assay; D000511:alpha-Macroglobulins / Q000032:analysis*
D015850:Interleukin-6; D000511:alpha-Macroglobulins