| Title |
Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease
|
|---|---|
| Published in |
Nature Neuroscience, October 2008
|
| DOI | 10.1038/nn.2213 |
| Pubmed ID | |
| Authors |
Rene O Sanchez-Mejia, John W Newman, Sandy Toh, Gui-Qiu Yu, Yungui Zhou, Brian Halabisky, Moustapha Cissé, Kimberly Scearce-Levie, Irene H Cheng, Li Gan, Jorge J Palop, Joseph V Bonventre, Lennart Mucke |
| Abstract |
Neuronal expression of familial Alzheimer's disease-mutant human amyloid precursor protein (hAPP) and hAPP-derived amyloid-beta (Abeta) peptides causes synaptic dysfunction, inflammation and abnormal cerebrovascular tone in transgenic mice. Fatty acids may be involved in these processes, but their contribution to Alzheimer's disease pathogenesis is uncertain. We used a lipidomics approach to generate a broad profile of fatty acids in brain tissues of hAPP-expressing mice and found an increase in arachidonic acid and its metabolites, suggesting increased activity of the group IV isoform of phospholipase A(2) (GIVA-PLA(2)). The levels of activated GIVA-PLA(2) in the hippocampus were increased in individuals with Alzheimer's disease and in hAPP mice. Abeta caused a dose-dependent increase in GIVA-PLA(2) phosphorylation in neuronal cultures. Inhibition of GIVA-PLA(2) diminished Abeta-induced neurotoxicity. Genetic ablation or reduction of GIVA-PLA(2) protected hAPP mice against Abeta-dependent deficits in learning and memory, behavioral alterations and premature mortality. Inhibition of GIVA-PLA(2) may be beneficial in the treatment and prevention of Alzheimer's disease. |
Mendeley readers
The data shown below were compiled from readership statistics for 277 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 4 | 1% |
| United States | 4 | 1% |
| Spain | 2 | <1% |
| Japan | 2 | <1% |
| Austria | 1 | <1% |
| Canada | 1 | <1% |
| South Africa | 1 | <1% |
| Netherlands | 1 | <1% |
| Malaysia | 1 | <1% |
| Other | 0 | 0% |
| Unknown | 260 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 61 | 22% |
| Student > Ph. D. Student | 50 | 18% |
| Student > Master | 35 | 13% |
| Professor > Associate Professor | 23 | 8% |
| Professor | 22 | 8% |
| Other | 54 | 19% |
| Unknown | 32 | 12% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 104 | 38% |
| Neuroscience | 51 | 18% |
| Medicine and Dentistry | 37 | 13% |
| Biochemistry, Genetics and Molecular Biology | 11 | 4% |
| Chemistry | 7 | 3% |
| Other | 24 | 9% |
| Unknown | 43 | 16% |
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 22 March 2022.
All research outputs
#4,551,421
of 23,390,392 outputs
Outputs from Nature Neuroscience
#3,151
of 5,294 outputs
Outputs of similar age
#15,650
of 92,256 outputs
Outputs of similar age from Nature Neuroscience
#15
of 37 outputs
Altmetric has tracked 23,390,392 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 5,294 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 54.0. This one is in the 38th percentile – i.e., 38% 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 92,256 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 81% of its contemporaries.
We're also able to compare this research output to 37 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.