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Divergent patterns of TDP-43 and tau pathologies in primary progressive aphasia
Giannini LAA, Xie SX, McMillan CT, Liang M, Williams A, Jester C, Rascovsky K, Wolk DA et al.. Annals of neurology, 2019-03-28
Topic: Brain proteins, microglia and lab models
Objective To measure postmortem burden of frontotemporal lobar degeneration (FTLD) with TDP-43 (FTLD-TDP) or tau (FTLD-Tau) proteinopathy across hemispheres in primary progressive aphasia (PPA) using digital histopathology and to identify clinicopathological correlates of these distinct proteinopathies. Methods In an autopsy cohort of PPA (FTLD-TDP = 13, FTLD-Tau = 14), we analyzed laterality and regional distribution of postmortem pathology, quantified using a validated digital histopathological approach, in available brain tissue from up to 8 cortical regions bilaterally. We related digital pathology to antemortem structural neuroimaging and specific clinical language features. Results Postmortem cortical pathology was left-lateralized in both FTLD-TDP (beta = -0.15, standard error [SE] = 0.05, p = 0.007) and FTLD-Tau (beta = -0.09, SE = 0.04, p = 0.015), but the degree of lateralization decreased with greater overall dementia severity before death (beta = -8.18, SE = 3.22, p = 0.015). Among 5 core pathology regions sampled, we found greatest pathology in left orbitofrontal cortex (OFC) in FTLD-TDP, which was greater than in FTLD-Tau (F = 47.07, df = 1,17, p Interpretation In PPA, FTLD-TDP and FTLD-Tau have divergent anatomic distributions of left-lateralized postmortem pathology that relate to antemortem structural imaging and distinct language deficits. Although other brain regions may be implicated in neural networks supporting these complex language measures, our observations may eventually help to improve antemortem diagnosis of neuropathology in PPA. Ann Neurol 2019;85:630-643.
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APA 7th
Giannini, L. A. A., Xie, S. X., McMillan, C. T., Liang, M., Williams, A., Jester, C., et al. (2019). Divergent patterns of TDP-43 and tau pathologies in primary progressive aphasia. Annals of neurology. https://doi.org/10.1002/ana.25465
Vancouver
Giannini LAA, Xie SX, McMillan CT, Liang M, Williams A, Jester C, et al. Divergent patterns of TDP-43 and tau pathologies in primary progressive aphasia. Annals of neurology. 2019. doi:10.1002/ana.25465. PMID: 30851133.
BibTeX
@article{giannini2019-30851133,
author = {Giannini, L. A. A. and Xie, S. X. and McMillan, C. T. and Liang, M. and Williams, A. and Jester, C. and Rascovsky, K. and Wolk, D. A. and others},
title = {{Divergent patterns of TDP-43 and tau pathologies in primary progressive aphasia}},
journal = {Annals of neurology},
year = {2019},
doi = {10.1002/ana.25465},
pmid = {30851133},
url = {https://doi.org/10.1002/ana.25465}
}
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Key findings
- Results Postmortem cortical pathology was left-lateralized in both FTLD-TDP (beta = -0.15, standard error [SE] = 0.05, p = 0.007) and FTLD-Tau (beta = -0.09, SE = 0.04, p = 0.015), but the degree of lateralization decreased with greater overall dementia severity before death (beta = -8.18, SE = 3.22, p = 0.015).
- Among 5 core pathology regions sampled, we found greatest pathology in left orbitofrontal cortex (OFC) in FTLD-TDP, which was greater than in FTLD-Tau (F = 47.07, df = 1,17, p < 0.001), and in left midfrontal cortex (MFC) in FTLD-Tau, which was greater than in FTLD-TDP (F = 19.34, df = 1,16, p < 0.001).
Why it matters
In people with primary progressive aphasia, two different proteins (TDP-43 and tau) build up mostly on the left side of the brain, and this left-sided pattern becomes less pronounced as overall dementia gets worse. The two proteins also differ in which brain regions they affect most, which may help explain different language problems, but this is an autopsy study and does not test any treatment.
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Study details
- Evidence strengthModerate
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 (Annals of neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (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 | 2 / 5 | 2019 — within 10 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 | 4 / 7 | Cited 55 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.1 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 3 / 6 | Cited 5.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 17 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 | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30851133) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
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