| Title |
Presynaptic proteins complexin-I and complexin-II differentially influence cognitive function in early and late stages of Alzheimer’s disease
|
|---|---|
| Published in |
Acta Neuropathologica, November 2016
|
| DOI | 10.1007/s00401-016-1647-9 |
| Pubmed ID | |
| Authors |
Alfredo Ramos-Miguel, Ken Sawada, Andrea A. Jones, Allen E. Thornton, Alasdair M. Barr, Sue E. Leurgans, Julie A. Schneider, David A. Bennett, William G. Honer |
| Abstract |
Progressive accumulation of Alzheimer's disease-related pathology is associated with cognitive dysfunction. Differences in cognitive reserve may contribute to individual differences in cognitive function in the presence of comparable neuropathology. The protective effects of cognitive reserve could contribute differentially in early versus late stages of the disease. We investigated presynaptic proteins as measures of brain reserve (a subset of total cognitive reserve), and used Braak staging to estimate the progression of Alzheimer's disease. Antemortem evaluations of cognitive function, postmortem assessments of pathologic indices, and presynaptic protein analyses, including the complexins I and II as respective measures of inhibitory and excitatory terminal function, were assayed in multiple key brain regions in 418 deceased participants from a community study. After covarying for demographic variables, pathologic indices, and overall synapse density, lower brain complexin-I and -II levels contributed to cognitive dysfunction (P < 0.01). Each complexin appeared to be dysregulated at a different Braak stage. Inhibitory complexin-I explained 14.4% of the variance in global cognition in Braak 0-II, while excitatory complexin-II explained 7.3% of the variance in Braak V-VI. Unlike other presynaptic proteins, complexins did not colocalize with pathologic tau within neuritic plaques, suggesting that these functional components of the synaptic machinery are cleared early from dystrophic neurites. Moreover, complexin levels showed distinct patterns of change related to memory challenges in a rat model, supporting the functional specificity of these proteins. The present results suggest that disruption of inhibitory synaptic terminals may trigger early cognitive impairment, while excitatory terminal disruption may contribute relatively more to later cognitive impairment. |
Mendeley readers
The data shown below were compiled from readership statistics for 67 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 67 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 11 | 16% |
| Student > Master | 10 | 15% |
| Researcher | 9 | 13% |
| Student > Bachelor | 5 | 7% |
| Other | 3 | 4% |
| Other | 8 | 12% |
| Unknown | 21 | 31% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 9 | 13% |
| Psychology | 8 | 12% |
| Medicine and Dentistry | 7 | 10% |
| Biochemistry, Genetics and Molecular Biology | 5 | 7% |
| Agricultural and Biological Sciences | 5 | 7% |
| Other | 11 | 16% |
| Unknown | 22 | 33% |
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 25 November 2016.
All research outputs
#4,195,563
of 22,903,988 outputs
Outputs from Acta Neuropathologica
#966
of 2,374 outputs
Outputs of similar age
#81,727
of 415,305 outputs
Outputs of similar age from Acta Neuropathologica
#21
of 32 outputs
Altmetric has tracked 22,903,988 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 2,374 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.3. This one has gotten more attention than average, scoring higher than 56% of its peers.
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