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Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis
Brettschneider J, Libon DJ, Toledo JB, Xie SX, McCluskey L, Elman L, Geser F, Lee VM et al.. Acta neuropathologica, 2012-01-01
Topic: Brain proteins, microglia and lab models
While cognitive deficits are increasingly recognized as common symptoms in amyotrophic lateral sclerosis (ALS), the underlying histopathologic basis for this is not known, nor has the relevance of neuroinflammatory mechanisms and microglial activation to cognitive impairment (CI) in ALS been systematically analyzed. Staining for neurodegenerative disease pathology, TDP-43, and microglial activation markers (CD68, Iba1) was performed in 102 autopsy cases of ALS, and neuropathology data were related to clinical and neuropsychological measures. ALS with dementia (ALS-D) and ALS with impaired executive function (ALS-Ex) patients showed significant microglial activation in middle frontal and superior or middle temporal (SMT) gyrus regions, as well as significant neuronal loss and TDP-43 pathology in these regions.
Key findings
- Staining for neurodegenerative disease pathology, TDP-43, and microglial activation markers (CD68, Iba1) was performed in 102 autopsy cases of ALS, and neuropathology data were related to clinical and neuropsychological measures.
- ALS with dementia (ALS-D) and ALS with impaired executive function (ALS-Ex) patients showed significant microglial activation in middle frontal and superior or middle temporal (SMT) gyrus regions, as well as significant neuronal loss and TDP-43 pathology in these regions.
- Microglial activation and TDP-43 pathology in middle frontal and superior or middle temporal regions were highly correlated with measures of executive impairment, but not with the MMSE.
- In contrast, only one ALS-D patient showed moderate Alzheimer's disease (AD) pathology.
Why it matters
This study examined brain tissue from 102 autopsy cases of amyotrophic lateral sclerosis and related microglial activation and TDP-43 pathology to cognitive measures. It is about the brain basis of cognitive problems in ALS and does not test any treatment, cure, or prevention for Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Acta neuropathologica) |
| Journal's citation record | 3 / 4 | Acta Neuropathologica: journal h-index 287 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 143 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.9 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 3 / 6 | Cited 5.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 2 / 4 | Cited 30 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author John Q. Trojanowski: h-index 255 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22210083) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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APA 7th
Brettschneider, J., Libon, D. J., Toledo, J. B., Xie, S. X., McCluskey, L., Elman, L., et al. (2012). Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis. Acta neuropathologica. https://doi.org/10.1007/s00401-011-0932-x
Vancouver
Brettschneider J, Libon DJ, Toledo JB, Xie SX, McCluskey L, Elman L, et al. Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis. Acta neuropathologica. 2012. doi:10.1007/s00401-011-0932-x. PMID: 22210083.
BibTeX
@article{brettschneider2012-22210083,
author = {Brettschneider, J. and Libon, D. J. and Toledo, J. B. and Xie, S. X. and McCluskey, L. and Elman, L. and Geser, F. and Lee, V. M. and others},
title = {{Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis}},
journal = {Acta neuropathologica},
year = {2012},
doi = {10.1007/s00401-011-0932-x},
pmid = {22210083},
url = {https://doi.org/10.1007/s00401-011-0932-x}
}
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