Feng-Qin Zhou, Juan Jiang, Chelsea M. Griffith, Peter R. Patrylo, Huaibin Cai, Yaping Chu, Xiao-Xin Yan
Abstract
Alzheimer's disease (AD) is a devastating neurodegenerative disorder bearing multiple pathological hallmarks suggestive of complex cellular/molecular interplay during pathogenesis. Transgenic mice and nonhuman primates are used as disease models for mechanistic and translational research into AD; the extent to which these animal models recapitulate AD-type neuropathology is an issue of importance. Putative C-terminal fragments from sortilin, a member of the vacuolar protein sorting 10 protein (Vps10p) family, have recently been shown to deposit in the neuritic β-amyloid (Aβ) plaques in the human brain.
We set out to explore if extracellular sortilin neuropathology exists in AD-related transgenic mice and nonhuman primates. Brains from different transgenic strains and ages developed overt cerebral Aβ deposition, including the β-amyloid precursor protein and presenilin 1 double-transgenic (APP/PS1) mice at ~ 14 months of age, the five familial Alzheimer's disease mutations transgenic (5×FAD) mice at ~ 8 months, the triple-transgenic Alzheimer's disease (3×Tg-AD) mice at ~ 22 months, and aged monkeys (Macaca mulatta and Macaca fascicularis) were examined. Brain samples from young transgenic mice, middle-aged/aged monkeys, and AD humans were used as negative and positive pathological controls.
The C-terminal sortilin antibody, which labeled senile plaques in the AD human cerebral sections, did not display extracellular immunolabeling in the transgenic mouse or aged monkey brain sections with Aβ deposition. In Western blot analysis, sortilin fragments ~ 15 kDa were not detectable in transgenic mouse cortical lysates, but they occurred in control AD lysates.
In reference to their human brain counterparts, neuritic plaques seen in transgenic AD model mouse brains represent an incomplete form of this AD pathological hallmark. The species difference in neuritic plaque constituents also indicates more complex secondary proteopathies in the human brain relative to rodents and nonhuman primates during aging and in AD.
Pharmacology, Toxicology and Pharmaceutical Science
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4%
Other
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19%
Unknown
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Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 7. 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 27 April 2018.
All research outputs
#4,230,289
of 23,045,021 outputs
Outputs from Alzheimer's Research & Therapy
#920
of 1,246 outputs
Outputs of similar age
#83,017
of 326,487 outputs
Outputs of similar age from Alzheimer's Research & Therapy
#18
of 24 outputs
Altmetric has tracked 23,045,021 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,246 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 25.9. This one is in the 20th percentile – i.e., 20% of its peers scored the same or lower than it.
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We're also able to compare this research output to 24 others from the same source and published within six weeks on either side of this one. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.
