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Clathrin adaptor CALM/PICALM is associated with neurofibrillary tangles and is cleaved in Alzheimer’s brains

Overview of attention for article published in Acta Neuropathologica, April 2013
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Title
Clathrin adaptor CALM/PICALM is associated with neurofibrillary tangles and is cleaved in Alzheimer’s brains
Published in
Acta Neuropathologica, April 2013
DOI 10.1007/s00401-013-1111-z
Pubmed ID
Authors

Kunie Ando, Jean-Pierre Brion, Virginie Stygelbout, Valérie Suain, Michèle Authelet, Robert Dedecker, Anaïs Chanut, Pascale Lacor, Jérémie Lavaur, Véronique Sazdovitch, Ekaterina Rogaeva, Marie-Claude Potier, Charles Duyckaerts

Abstract

PICALM, a clathrin adaptor protein, plays important roles in clathrin-mediated endocytosis in all cell types. Recently, genome-wide association studies identified single nucleotide polymorphisms in PICALM gene as genetic risk factors for late-onset Alzheimer disease (LOAD). We analysed by western blotting with several anti-PICALM antibodies the pattern of expression of PICALM in human brain extracts. We found that PICALM was abnormally cleaved in AD samples and that the level of the uncleaved 65-75 kDa full-length PICALM species was significantly decreased in AD brains. Cleavage of human PICALM after activation of endogenous calpain or caspase was demonstrated in vitro. Immunohistochemistry revealed that PICALM was associated in situ with neurofibrillary tangles, co-localising with conformationally abnormal and hyperphosphorylated tau in LOAD, familial AD and Down syndrome cases. PHF-tau proteins co-immunoprecipitated with PICALM. PICALM was highly expressed in microglia in LOAD. These observations suggest that PICALM is associated with the development of AD tau pathology. PICALM cleavage could contribute to endocytic dysfunction in AD.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 132 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
Unknown 131 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 31 23%
Researcher 21 16%
Student > Master 15 11%
Student > Bachelor 10 8%
Professor 8 6%
Other 21 16%
Unknown 26 20%
Readers by discipline Count As %
Agricultural and Biological Sciences 34 26%
Neuroscience 21 16%
Biochemistry, Genetics and Molecular Biology 17 13%
Medicine and Dentistry 10 8%
Pharmacology, Toxicology and Pharmaceutical Science 3 2%
Other 11 8%
Unknown 36 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 19 April 2013.
All research outputs
#18,336,865
of 22,707,247 outputs
Outputs from Acta Neuropathologica
#2,194
of 2,360 outputs
Outputs of similar age
#132,432
of 175,235 outputs
Outputs of similar age from Acta Neuropathologica
#14
of 16 outputs
Altmetric has tracked 22,707,247 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,360 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.3. This one is in the 3rd percentile – i.e., 3% of its peers scored the same or lower than it.
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We're also able to compare this research output to 16 others from the same source and published within six weeks on either side of this one. This one is in the 6th percentile – i.e., 6% of its contemporaries scored the same or lower than it.