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Frontotemporal lobar degeneration proteinopathies have disparate microscopic patterns of white and grey matter pathology
Giannini LAA, Peterson C, Ohm D, Xie SX, McMillan CT, Raskovsky K, Massimo L, Suh E et al.. Acta neuropathologica communications, 2021-02-23
Topic: Brain proteins, microglia and lab models
Frontotemporal lobar degeneration proteinopathies with tau inclusions (FTLD-Tau) or TDP-43 inclusions (FTLD-TDP) are associated with clinically similar phenotypes. However, these disparate proteinopathies likely differ in cellular severity and regional distribution of inclusions in white matter (WM) and adjacent grey matter (GM), which have been understudied. We performed a neuropathological study of subcortical WM and adjacent GM in a large autopsy cohort (n = 92; FTLD-Tau = 37, FTLD-TDP = 55) using a validated digital image approach. The antemortem clinical phenotype was behavioral-variant frontotemporal dementia (bvFTD) in 23 patients with FTLD-Tau and 42 with FTLD-TDP, and primary progressive aphasia (PPA) in 14 patients with FTLD-Tau and 13 with FTLD-TDP. We used linear mixed-effects models to: (1) compare WM pathology burden between proteinopathies; (2) investigate the relationship between WM pathology burden and WM degeneration using luxol fast blue (LFB) myelin staining; (3) study regional patterns of pathology burden in clinico-pathological groups. WM pathology burden was greater in FTLD-Tau compared to FTLD-TDP across regions (beta = 4.21, SE = 0.34, p < 0.001), and correlated with the degree of WM degeneration in both FTLD-Tau (beta = 0.32, SE = 0.10, p = 0.002) and FTLD-TDP (beta = 0.40, SE = 0.08, p < 0.001). WM degeneration was greater in FTLD-Tau than FTLD-TDP particularly in middle-frontal and anterior cingulate regions (p < 0.05). Distinct regional patterns of WM and GM inclusions characterized FTLD-Tau and FTLD-TDP proteinopathies, and associated in part with clinical phenotype. In FTLD-Tau, WM pathology was particularly severe in the dorsolateral frontal cortex in nonfluent-variant PPA, and GM pathology in dorsolateral and paralimbic frontal regions with some variation across tauopathies. Differently, FTLD-TDP had little WM regional variability, but showed severe GM pathology burden in ventromedial prefrontal regions in both bvFTD and PPA. To conclude, FTLD-Tau and FTLD-TDP proteinopathies have distinct severity and regional distribution of WM and GM pathology, which may impact their clinical presentation, with overall greater severity of WM pathology as a distinguishing feature of tauopathies.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Giannini, L. A. A., Peterson, C., Ohm, D., Xie, S. X., McMillan, C. T., Raskovsky, K., et al. (2021). Frontotemporal lobar degeneration proteinopathies have disparate microscopic patterns of white and grey matter pathology. Acta neuropathologica communications. https://doi.org/10.1186/s40478-021-01129-2
Vancouver
Giannini LAA, Peterson C, Ohm D, Xie SX, McMillan CT, Raskovsky K, et al. Frontotemporal lobar degeneration proteinopathies have disparate microscopic patterns of white and grey matter pathology. Acta neuropathologica communications. 2021. doi:10.1186/s40478-021-01129-2. PMID: 33622418.
BibTeX
@article{giannini2021-33622418,
author = {Giannini, L. A. A. and Peterson, C. and Ohm, D. and Xie, S. X. and McMillan, C. T. and Raskovsky, K. and Massimo, L. and Suh, E. and others},
title = {{Frontotemporal lobar degeneration proteinopathies have disparate microscopic patterns of white and grey matter pathology}},
journal = {Acta neuropathologica communications},
year = {2021},
doi = {10.1186/s40478-021-01129-2},
pmid = {33622418},
url = {https://doi.org/10.1186/s40478-021-01129-2}
}
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.
Key findings
- Frontotemporal lobar degeneration proteinopathies with tau inclusions (FTLD-Tau) or TDP-43 inclusions (FTLD-TDP) are associated with clinically similar phenotypes.
- WM pathology burden was greater in FTLD-Tau compared to FTLD-TDP across regions (beta = 4.21, SE = 0.34, p < 0.001), and correlated with the degree of WM degeneration in both FTLD-Tau (beta = 0.32, SE = 0.10, p = 0.002) and FTLD-TDP (beta = 0.40, SE = 0.08, p < 0.001).
- To conclude, FTLD-Tau and FTLD-TDP proteinopathies have distinct severity and regional distribution of WM and GM pathology, which may impact their clinical presentation, with overall greater severity of WM pathology as a distinguishing feature of tauopathies.
Why it matters
In an autopsy cohort, frontotemporal lobar degeneration with tau inclusions and with TDP-43 inclusions showed different patterns of white and grey matter pathology despite similar clinical symptoms. This is a neuropathological study and reports no treatment or prevention.
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Study details
- Participants92
- Evidence strengthModerate
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta neuropathologica communications) |
| Journal's citation record | 1 / 4 | Acta Neuropathologica Communications: journal h-index 129 (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 | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 92 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 | 3 / 7 | Cited 39 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.6 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 4.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 16 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author David John Irwin: h-index 76 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33622418) |
| Free to read | 2 / 2 | Free to read |
| Total | 49 / 100 | — |
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Read the original
- DOI: 10.1186/s40478-021-01129-2
- PubMed: 33622418
- Original source →
- Free full text: Acta Neuropathologica Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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