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Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD)
Brettschneider J, Del Tredici K, Irwin DJ, Grossman M, Robinson JL, Toledo JB, Fang L, Van Deerlin VM et al.. Acta neuropathologica, 2014-01-10
Topic: Brain proteins, microglia and lab models
We examined regional distribution patterns of phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) intraneuronal inclusions in frontotemporal lobar degeneration (FTLD). Immunohistochemistry was performed on 70 μm sections from FTLD-TDP autopsy cases (n = 39) presenting with behavioral variant frontotemporal dementia. Two main types of cortical pTDP-43 pathology emerged, characterized by either predominantly perikaryal pTDP-43 inclusions (cytoplasmic type, cFTLD) or long aggregates in dendrites (neuritic type, nFTLD). Cortical involvement in nFTLD was extensive and frequently reached occipital areas, whereas cases with cFTLD often involved bulbar somatomotor neurons and the spinal cord. We observed four patterns indicative of potentially sequential dissemination of pTDP-43: cases with the lowest burden of pathology (pattern I) were characterized by widespread pTDP-43 lesions in the orbital gyri, gyrus rectus, and amygdala. With increasing burden of pathology (pattern II) pTDP-43 lesions emerged in the middle frontal and anterior cingulate gyrus as well as in anteromedial temporal lobe areas, the superior and medial temporal gyri, striatum, red nucleus, thalamus, and precerebellar nuclei. More advanced cases showed a third pattern (III) with involvement of the motor cortex, bulbar somatomotor neurons, and the spinal cord anterior horn, whereas cases with the highest burden of pathology (pattern IV) were characterized by pTDP-43 lesions in the visual cortex. We interpret the four neuropathological patterns in bvFTD to be consistent with the hypothesis that pTDP-43 pathology can spread sequentially and may propagate along axonal pathways.
Key findings
- We observed four patterns indicative of potentially sequential dissemination of pTDP-43: cases with the lowest burden of pathology (pattern I) were characterized by widespread pTDP-43 lesions in the orbital gyri, gyrus rectus, and amygdala.
Why it matters
This autopsy study of 39 brains found that a protein called pTDP-43 spreads through the brain in four patterns that seem to follow a sequence in a type of frontotemporal dementia. This describes how the disease progresses but does not test any treatment, so it does not yet show how to treat, cure or prevent dementia.
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Study details
- Participants39
- Evidence strengthLow
How this study scored 57/100
Published in a leading specialty journal. Scored zero for study design, effect reported 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 | 2014 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 39 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 314 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.4 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 4 / 6 | Cited 17.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 22 other studies in this library |
| Still being cited | 3 / 4 | Cited 58 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 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24407427) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
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Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Brettschneider, J., Del Tredici, K., Irwin, D. J., Grossman, M., Robinson, J. L., Toledo, J. B., et al. (2014). Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD). Acta neuropathologica. https://doi.org/10.1007/s00401-013-1238-y
Vancouver
Brettschneider J, Del Tredici K, Irwin DJ, Grossman M, Robinson JL, Toledo JB, et al. Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD). Acta neuropathologica. 2014. doi:10.1007/s00401-013-1238-y. PMID: 24407427.
BibTeX
@article{brettschneider2014-24407427,
author = {Brettschneider, J. and Del Tredici, K. and Irwin, D. J. and Grossman, M. and Robinson, J. L. and Toledo, J. B. and Fang, L. and Van Deerlin, V. M. and others},
title = {{Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD)}},
journal = {Acta neuropathologica},
year = {2014},
doi = {10.1007/s00401-013-1238-y},
pmid = {24407427},
url = {https://doi.org/10.1007/s00401-013-1238-y}
}
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