Premium
P3‐392: Induction of neuronal tau expression by conditioned medium from activated microglial cells
Author(s) -
Lee Moonhee,
Schwab Claudia,
Yu Sheng,
McGeer Edith,
McGeer Patrick
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.2066
Subject(s) - microglia , tau protein , immunostaining , proinflammatory cytokine , downregulation and upregulation , gene isoform , microbiology and biotechnology , chemistry , blot , neurodegeneration , cytokine , phosphorylation , biology , immunology , alzheimer's disease , medicine , immunohistochemistry , biochemistry , inflammation , disease , gene
Background: The major hallmark of tauopathies, including Alzheimer’s disease (AD), is the accumulation of neurofibrillary tangles (NFTs). These are aggregates of tau which develop intracellularly, eventually causing the neurons to die. Since the tau is phosphorylated, it has generally been considered that the phosphorylation causes the aggregation. Another potential cause, which is relatively unexplored, is that neurons under stress, as occurs in AD from activated microglia, upregulate expression of tau and that excessive tau is the cause. We explored this possibility by measuring the levels of tau expression in human neurons following exposure to medium from stimulated human microglia. Methods: We exposed both differentiated NT-2 cells and SH-SY5Y cells to conditioned medium from human microglia that had been stimulated for 2 days with LPS/IFN g. We measured the expression levels of total tau and tau isoforms byWestern blotting and fluorescence-labelled immunostaining with anti-human tau antibodies. We compared these levels with that of tubulin, the protein that tau normally binds to in vivo. Results: Increased expression of total tau, with the same of 3R/4R isoform distribution found in AD was observed in both NT-2 cells and SH-SY5Y cells following incubation in conditioned medium from human microglia. There was no upregulation of tubulin. Treatment of microglia with A b proteins (10 ng/ml) and proinflammatory cytokines such as IL-6 and IL-1 b (1 ng/ml each) also increased tau expression, but TNFa did not. However treatment with an anti-inflammatory cytokine IL-10 attenuated the increase in tau expression. Conclusions: Activated microglia can secrete inflammatory components which upregulate expression of 3R/ 4R tau but not tubulin. An excess of tau upregulated in this manner may be the cause of neurofibrillary tangle development in AD.