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Tau passive immunization inhibits not only tau but also Aβ pathology

Overview of attention for article published in Alzheimer's Research & Therapy, January 2017
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  • Above-average Attention Score compared to outputs of the same age (55th percentile)

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Title
Tau passive immunization inhibits not only tau but also Aβ pathology
Published in
Alzheimer's Research & Therapy, January 2017
DOI 10.1186/s13195-016-0227-5
Pubmed ID
Authors

Chun-ling Dai, Yunn Chyn Tung, Fei Liu, Cheng-Xin Gong, Khalid Iqbal

Abstract

Accumulation of hyperphosphorylated tau protein is a histopathological hallmark of Alzheimer's disease (AD) and related tauopathies. Currently, there is no effective treatment available for these progressive neurodegenerative diseases. In recent years, tau immunotherapy has shown great potential in animal models. We report the effect of immunization with tau antibodies 43D against tau 6-18 and 77E9 against tau 184-195 on tau and amyloid-β (Aβ) pathologies and cognition in triple-transgenic (3×Tg)-AD mice at mild to moderate stages of the disease. We immunized 12-month-old female 3×Tg-AD mice with two to six or seven intravenous weekly doses of 15 μg of mouse monoclonal antibody 43D, 77E9, a combination of one-half dose each of 43D and 77E9, or as control of mouse immunoglobulin G (IgG). Age-matched wild-type mice treated with mouse IgG or a mixture of 43D and 77E9 were also used as controls. The effect of immunization with tau antibodies on tau and Aβ pathologies was assessed by Western blot and immunofluorescence analysis, and the effect on cognition was analyzed by using Morris water maze, one-trial novel object recognition, and novel object location tasks. We found that two doses of 43D and 77E9 reduced total tau but had no significant impact on hyperphosphorylation of tau. However, six doses of 43D reduced levels of both total tau and tau hyperphosphorylated at Ser262/356 and Ser396/404 sites in the hippocampus. Importantly, both 43D and 77E9 antibodies rescued spatial memory and short-term memory impairments in 3×Tg-AD mice. The beneficial effect of 43D and 77E9 antibodies on cognitive performance was sustained up to 3 months after the last dose. Six doses of immunization with 43D also decreased amyloid precursor protein (APP) level in CA1 and amyloid plaques in subiculum, and showed a trend toward reducing Aβ40 and Aβ42 in the forebrain. Immunization with 43D increased levels of complement components C1 and C9 and resulted in activation of microglia, especially surrounding Aβ plaques. These findings suggest the potential of passive immunization targeting proximal N-terminal domain tau 6-18 as a disease-modifying approach to AD and related tauopathies.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 122 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 <1%
United States 1 <1%
Unknown 120 98%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 28 23%
Researcher 23 19%
Student > Ph. D. Student 13 11%
Student > Doctoral Student 11 9%
Student > Master 11 9%
Other 15 12%
Unknown 21 17%
Readers by discipline Count As %
Neuroscience 26 21%
Agricultural and Biological Sciences 19 16%
Biochemistry, Genetics and Molecular Biology 16 13%
Medicine and Dentistry 12 10%
Pharmacology, Toxicology and Pharmaceutical Science 7 6%
Other 15 12%
Unknown 27 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 April 2017.
All research outputs
#6,118,618
of 11,374,283 outputs
Outputs from Alzheimer's Research & Therapy
#333
of 446 outputs
Outputs of similar age
#136,092
of 321,157 outputs
Outputs of similar age from Alzheimer's Research & Therapy
#12
of 12 outputs
Altmetric has tracked 11,374,283 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 446 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 16.5. This one is in the 24th percentile – i.e., 24% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 321,157 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.
We're also able to compare this research output to 12 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.