Repeated immunization of mice with phosphorylated-tau peptides causes neuroinflammation.
Τίτλος | Repeated immunization of mice with phosphorylated-tau peptides causes neuroinflammation. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Rozenstein-Tsalkovich, L., Grigoriadis N., Lourbopoulos A., Nousiopoulou E., Kassis I., Abramsky O., Karussis D., & Rosenmann H. |
Journal | Exp Neurol |
Volume | 248 |
Pagination | 451-6 |
Date Published | 2013 Oct |
ISSN | 1090-2430 |
Λέξεις κλειδιά | Animals, Brain, Disease Models, Animal, Encephalitis, Immunization, Immunotherapy, Neurofibrillary Tangles, Neurons, Phosphorylation, tau Proteins, Tauopathies |
Abstract | The recent studies of others and of us showing robust efficacy of anti-tangle immunotherapy, directed against phosphorylated (phos)-tau protein, may pave the way to clinical trials of phos-tau immunotherapy in Alzheimer's-disease and other tauopathies. At this stage addressing the safety of the phos-tau-immunotherapy is highly needed, particularly since we have previously shown the neurotoxic potential of tau-immunotherapy, specifically of full-length unphosphorylated-tau vaccine under a CNS-proinflammatory milieu [induced by emulsification in complete-Freund's-adjuvant (CFA) and pertussis-toxin (PT)] in young wild-type (WT)-mice. The aim of our current study was to address safety aspects of the phos-tau-immunotherapy in both neurofibrillary-tangle (NFT)-mice as well as in WT-mice, under challenging conditions of repeated immunizations with phos-tau peptides under a CNS-proinflammatory milieu. NFT- and WT-mice were repeatedly immunized (7 injections in adult-, 4 in aged-mice) with phos-tau peptides emulsified in CFA-PT. A paralytic disease was evident in the phos-tau-immunized adult NFT-mice, developing progressively to 26.7% with the number of injections. Interestingly, the WT-mice were even more prone to develop neuroinflammation following phos-tau immunization, affecting 75% of the immunized mice. Aged mice were less prone to neuroinflammatory manifestations. Anti-phos-tau antibodies, detected in the serum of immunized mice, partially correlated with the neuroinflammation in WT-mice. This points that repeated phos-tau immunizations in the frame of a proinflammatory milieu may be encephalitogenic to tangle-mice, and more robustly to WT-mice, indicating that - under certain conditions - the safety of phos-tau immunotherapy is questionable. |
DOI | 10.1016/j.expneurol.2013.07.006 |
Alternate Journal | Exp. Neurol. |
PubMed ID | 23876516 |