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Neuropathological background of phenotypical variability in frontotemporal dementia
Josephs KA, Hodges JR, Snowden JS, Mackenzie IR, Neumann M, Mann DM, Dickson DW.. Acta neuropathologica, 2011-05-26
Topic: Risk, prevention and care in population studies
Frontotemporal lobar degeneration (FTLD) is the umbrella term encompassing a heterogeneous group of pathological disorders. With recent discoveries, the FTLDs have been show to classify nicely into three main groups based on the major protein deposited in the brain: FTLD-tau, FTLD-TDP and FTLD-FUS. These pathological groups, and their specific pathologies, underlie a number of well-defined clinical syndromes, including three frontotemporal dementia (FTD) variants [behavioral variant frontotemporal dementia (bvFTD), progressive non-fluent aphasia, and semantic dementia (SD)], progressive supranuclear palsy syndrome (PSPS) and corticobasal syndrome (CBS). Understanding the neuropathological background of the phenotypic variability in FTD, PSPS and CBS requires large clinicopathological studies. We review current knowledge on the relationship between the FTLD pathologies and clinical syndromes, and pool data from a number of large clinicopathological studies that collectively provide data on 544 cases. Strong relationships were identified as follows: FTD with motor neuron disease and FTLD-TDP; SD and FTLD-TDP; PSPS and FTLD-tau; and CBS and FTLD-tau. However, the relationship between some of these clinical diagnoses and specific pathologies is not so clear cut. In addition, the clinical diagnosis of bvFTD does not have a strong relationship to any FTLD subtype or specific pathology and therefore remains a diagnostic challenge. Some evidence suggests improved clinicopathological association of bvFTD by further refining clinical characteristics. Unlike FTLD-tau and FTLD-TDP, FTLD-FUS has been less well characterized, with only 69 cases reported. However, there appears to be some associations between clinical phenotypes and FTLD-FUS pathologies. Clinical diagnosis is therefore promising in predicting molecular pathology.
Key findings
- In addition, the clinical diagnosis of bvFTD does not have a strong relationship to any FTLD subtype or specific pathology and therefore remains a diagnostic challenge.
- Some evidence suggests improved clinicopathological association of bvFTD by further refining clinical characteristics.
- Unlike FTLD-tau and FTLD-TDP, FTLD-FUS has been less well characterized, with only 69 cases reported.
- However, there appears to be some associations between clinical phenotypes and FTLD-FUS pathologies.
- Clinical diagnosis is therefore promising in predicting molecular pathology.
Why it matters
This review describes how frontotemporal lobar degeneration is classified into FTLD-tau, FTLD-TDP, and FTLD-FUS, and how these relate to clinical syndromes. It notes that the clinical diagnosis of behavioral variant frontotemporal dementia does not have a strong relationship to any FTLD subtype or specific pathology, which is a diagnostic challenge rather than a treatment or cure.
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Study details
- Evidence strengthLow
How this study scored 57/100
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 | 2011 — 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 | 6 / 7 | Cited 464 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 27.3 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 5 / 6 | Cited 23.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 27 other studies in this library |
| Still being cited | 3 / 4 | Cited 71 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Dennis W. Dickson: h-index 218 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21614463) |
| Free to read | 2 / 2 | Free to read |
| Total | 57 / 100 | — |
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Read the original
- DOI: 10.1007/s00401-011-0839-6
- PubMed: 21614463
- Original source →
- Free full text: Acta Neuropathologica →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Josephs, K. A., Hodges, JR., Snowden, J. S., Mackenzie, I. R., Neumann, M., Mann, D. M., et al. (2011). Neuropathological background of phenotypical variability in frontotemporal dementia. Acta neuropathologica. https://doi.org/10.1007/s00401-011-0839-6
Vancouver
Josephs KA, Hodges JR, Snowden JS, Mackenzie IR, Neumann M, Mann DM, et al. Neuropathological background of phenotypical variability in frontotemporal dementia. Acta neuropathologica. 2011. doi:10.1007/s00401-011-0839-6. PMID: 21614463.
BibTeX
@article{josephs2011-21614463,
author = {Josephs, K. A. and Hodges, JR. and Snowden, J. S. and Mackenzie, I. R. and Neumann, M. and Mann, D. M. and Dickson, D. W.},
title = {{Neuropathological background of phenotypical variability in frontotemporal dementia}},
journal = {Acta neuropathologica},
year = {2011},
doi = {10.1007/s00401-011-0839-6},
pmid = {21614463},
url = {https://doi.org/10.1007/s00401-011-0839-6}
}
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