Tau-targeted immunization impedes progression of neurofibrillary histopathology in aged P301L tau transgenic mice

Bi, Mian, Ittner, Arne, Ke, Yazi D., Gotz, Jurgen and Ittner, Lars M. (2011) Tau-targeted immunization impedes progression of neurofibrillary histopathology in aged P301L tau transgenic mice. PLoS ONE, 6 12: e26860.1-e26860.7. doi:10.1371/journal.pone.0026860


Author Bi, Mian
Ittner, Arne
Ke, Yazi D.
Gotz, Jurgen
Ittner, Lars M.
Title Tau-targeted immunization impedes progression of neurofibrillary histopathology in aged P301L tau transgenic mice
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2011-12
Year available 2011
Sub-type Article (original research)
DOI 10.1371/journal.pone.0026860
Open Access Status DOI
Volume 6
Issue 12
Start page e26860.1
End page e26860.7
Total pages 7
Place of publication San Francisco, United States
Publisher Public Library of Science (PLoS)
Language eng
Abstract In Alzheimer's disease (AD) brains, the microtubule-associated protein tau and amyloid-β (Aβ) deposit as intracellular neurofibrillary tangles (NFTs) and extracellular plaques, respectively. Tau deposits are furthermore found in a significant number of frontotemporal dementia cases. These diseases are characterized by progressive neurodegeneration, the loss of intellectual capabilities and behavioral changes. Unfortunately, the currently available therapies are limited to symptomatic relief. While active immunization against Aβ has shown efficacy in both various AD mouse models and patients with AD, immunization against pathogenic tau has only recently been shown to prevent pathology in young tau transgenic mice. However, if translated to humans, diagnosis and treatment would be routinely done when symptoms are overt, meaning that the histopathological changes have already progressed. Therefore, we used active immunization to target pathogenic tau in 4, 8, and 18 months-old P301L tau transgenic pR5 mice that have an onset of NFT pathology at 6 months of age. In all age groups, NFT pathology was significantly reduced in treated compared to control pR5 mice. Similarly, phosphorylation of tau at pathological sites was reduced. In addition, increased astrocytosis was found in the oldest treated group. Taken together, our data suggests that tau-targeted immunization slows the progression of NFT pathology in mice, with practical implications for human patients.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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