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Increased expression of the lysosomal cholesterol transporter NPC1 in Alzheimer's disease

Overview of attention for article published in Biochimica et Biophysica Acta (BBA), May 2010
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Title
Increased expression of the lysosomal cholesterol transporter NPC1 in Alzheimer's disease
Published in
Biochimica et Biophysica Acta (BBA), May 2010
DOI 10.1016/j.bbalip.2010.05.005
Pubmed ID
Authors

Katarina Kågedal, Woojin Scott Kim, Hanna Appelqvist, Sharon Chan, Danni Cheng, Lotta Agholme, Kevin Barnham, Heather McCann, Glenda Halliday, Brett Garner

Abstract

The Niemann-Pick type C1 (NPC1) protein mediates the trafficking of cholesterol from lysosomes to other organelles. Mutations in the NPC1 gene lead to the retention of cholesterol and other lipids in the lysosomal compartment, and such defects are the basis of NPC disease. Several parallels exist between NPC disease and Alzheimer's disease (AD), including altered cholesterol homeostasis, changes in the lysosomal system, neurofibrillary tangles, and increased amyloid-beta generation. How the expression of NPC1 in the human brain is affected in AD has not been investigated so far. In the present study, we measured NPC1 mRNA and protein expression in three distinct regions of the human brain, and we revealed that NPC1 expression is upregulated at both mRNA and protein levels in the hippocampus and frontal cortex of AD patients compared to control individuals. In the cerebellum, a brain region that is relatively spared in AD, no difference in NPC1 expression was detected. Similarly, murine NPC1 mRNA levels were increased in the hippocampus of 12-month-old transgenic mice expressing a familial AD form of human amyloid-beta precursor protein (APP) and presenilin-1 (APP/PS1tg) compared to 12-month-old wild type mice, whereas no change in NPC1 was detected in mouse cerebellum. Immunohistochemical analysis of human hippocampus indicated that NPC1 expression was strongest in neurons. However, in vitro studies revealed that NPC1 expression was not induced by transfecting SK-N-SH neurons with human APP or by treating them with oligomeric amyloid-beta peptide. Total cholesterol levels were reduced in hippocampus from AD patients compared to control individuals, and it is therefore possible that the increased expression of NPC1 is linked to perturbed cholesterol homeostasis in AD.

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Mendeley readers

The data shown below were compiled from readership statistics for 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
Russia 1 2%
Unknown 48 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 22%
Researcher 8 16%
Student > Master 6 12%
Other 4 8%
Professor 3 6%
Other 7 14%
Unknown 11 22%
Readers by discipline Count As %
Agricultural and Biological Sciences 10 20%
Medicine and Dentistry 9 18%
Biochemistry, Genetics and Molecular Biology 6 12%
Psychology 2 4%
Neuroscience 2 4%
Other 6 12%
Unknown 15 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 18 October 2022.
All research outputs
#8,533,995
of 25,371,288 outputs
Outputs from Biochimica et Biophysica Acta (BBA)
#6,104
of 19,217 outputs
Outputs of similar age
#37,923
of 103,393 outputs
Outputs of similar age from Biochimica et Biophysica Acta (BBA)
#46
of 112 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 19,217 research outputs from this source. They receive a mean Attention Score of 4.4. This one is in the 15th percentile – i.e., 15% 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 103,393 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 22nd percentile – i.e., 22% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 112 others from the same source and published within six weeks on either side of this one. This one is in the 9th percentile – i.e., 9% of its contemporaries scored the same or lower than it.