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Polygenic analysis of inflammatory disease variants and effects on microglia in the aging brain

Overview of attention for article published in Molecular Neurodegeneration, July 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (85th percentile)
  • Good Attention Score compared to outputs of the same age and source (70th percentile)

Mentioned by

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1 news outlet
twitter
9 tweeters

Citations

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7 Dimensions

Readers on

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49 Mendeley
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Title
Polygenic analysis of inflammatory disease variants and effects on microglia in the aging brain
Published in
Molecular Neurodegeneration, July 2018
DOI 10.1186/s13024-018-0272-6
Pubmed ID
Authors

Daniel Felsky, Ellis Patrick, Julie A. Schneider, Sara Mostafavi, Chris Gaiteri, Nikolaos Patsopoulos, David A. Bennett, Philip L. De Jager

Abstract

The role of the innate immune system in Alzheimer's disease (AD) and neurodegenerative disease susceptibility has recently been highlighted in genetic studies. However, we do not know whether risk for inflammatory disease predisposes unaffected individuals to late-life cognitive deficits or AD-related neuropathology. We investigated whether genetic risk scores for seven immune diseases and central nervous system traits were related to cognitive decline (nmax = 1601), classical AD neuropathology (nmax = 985), or microglial density (nmax = 184). Longitudinal cognitive decline, postmortem amyloid and tau neuropathology, microglial density, and gene module expression from bulk brain tissue were all measured in participants from two large cohorts (the Rush Religious Orders Study and Memory and Aging Project; ROS/MAP) of elderly subjects (mean age at entry 78 +/- 8.7 years). We analyzed data primarily using robust regression methods. Neuropathologists were blind to clinical data. The AD genetic risk scores, including and excluding APOE effects, were strongly associated with cognitive decline in all domains (min Puncor = 3.2 × 10- 29). Multiple sclerosis (MS), Parkinson's disease, and schizophrenia risk did not influence cognitive decline in older age, but the rheumatoid arthritis (RA) risk score alone was significantly associated with microglial density after correction (t146 = - 3.88, Puncor = 1.6 × 10- 4). Post-hoc tests found significant effects of the RA genetic risk score in multiple regions and stages of microglial activation (min Puncor = 1.5 × 10- 6). However, these associations were driven by only one or two variants, rather than cumulative polygenicity. Further, individual MS (Pone-sided < 8.4 × 10- 4) and RA (Pone-sided = 3 × 10- 4) variants associated with higher microglial density were also associated with increased expression of brain immune gene modules. Our results demonstrate that global risk of inflammatory disease does not strongly influence aging-related cognitive decline but that susceptibility variants that influence peripheral immune function also alter microglial density and immune gene expression in the aging brain, opening a new perspective on the control of microglial and immune responses within the central nervous system. Further study on the molecular mechanisms of peripheral immune disease risk influencing glial cell activation will be required to identify key regulators of these pathways.

Twitter Demographics

The data shown below were collected from the profiles of 9 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 49 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 14 29%
Researcher 14 29%
Unspecified 6 12%
Student > Master 6 12%
Student > Bachelor 3 6%
Other 6 12%
Readers by discipline Count As %
Neuroscience 15 31%
Medicine and Dentistry 8 16%
Unspecified 7 14%
Biochemistry, Genetics and Molecular Biology 6 12%
Agricultural and Biological Sciences 5 10%
Other 8 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 13. 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 July 2018.
All research outputs
#1,132,617
of 13,288,667 outputs
Outputs from Molecular Neurodegeneration
#74
of 565 outputs
Outputs of similar age
#39,987
of 268,217 outputs
Outputs of similar age from Molecular Neurodegeneration
#3
of 10 outputs
Altmetric has tracked 13,288,667 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 565 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.5. This one has done well, scoring higher than 85% of its peers.
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 268,217 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 85% of its contemporaries.
We're also able to compare this research output to 10 others from the same source and published within six weeks on either side of this one. This one has scored higher than 7 of them.