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TDP-43-associated atrophy in brains with and without frontotemporal lobar degeneration
Marina Buciuc, Peter R Martin, Nirubol Tosakulwong, Melissa E Murray, Leonard Petrucelli, Matthew L Senjem, Anthony J Spychalla, David S Knopman et al.. NeuroImage. Clinical, 2022-02-04
Topic: Plasma and spinal-fluid biomarkers
Transactive response DNA-binding protein of ∼43 kDa (TDP-43), a primary pathologic substrate in tau-negative frontotemporal lobar degeneration (FTLD), is also often found in the brains of elderly individuals without FTLD and is a key player in the process of neurodegeneration in brains with and without FTLD. It is unknown how rates and trajectories of TDP-43-associated brain atrophy compare between these two groups. Additionally, non-FTLD TDP-43 inclusions are not homogeneous and can be divided into two morphologic types: type-α and neurofibrillary tangle-associated type-β. Therefore, we explored whether neurodegeneration also varies due to the morphologic type. In this longitudinal retrospective study of 293 patients with 843 MRI scans spanning over ∼10 years, we used a Bayesian hierarchical linear model to quantify similarities and differences between the non-FTLD TDP-43 (type-α/type-β) and FTLD-TDP (n = 68) in both regional volume at various timepoints before death and annualized rate of atrophy. Since Alzheimer's disease (AD) is a frequent co-pathology in non-FTLD TDP-43, we further divided types α/β based on presence/absence of intermediate-high likelihood AD: AD-TDP type-β (n = 90), AD-TDP type-α (n = 104), and Pure-TDP (n = 31, all type-α). FTLD-TDP was associated with faster atrophy rates in the inferior temporal lobe and temporal pole compared to all non-FTLD TDP-43 groups. The atrophy rate in the frontal lobe was modulated by age with younger FTLD-TDP having the fastest rates. Older FTLD-TDP showed a limbic predominant pattern of neurodegeneration. AD-TDP type-α showed faster rates of hippocampal atrophy and smaller volumes of amygdala, temporal pole, and inferior temporal lobe compared to AD-TDP type-β. Pure-TDP was associated with slowest rates and less atrophy in all brain regions. The results suggest that there are differences and similarities in longitudinal brain volume loss between FTLD-TDP and non-FTLD TDP-43. Within FTLD-TDP age plays a role in which brain regions are the most affected. Additionally, brain atrophy regional rates also vary by non-FTLD TDP-43 type.
Key findings
- FTLD-TDP was associated with faster atrophy rates in the inferior temporal lobe and temporal pole compared to all non-FTLD TDP-43 groups.
- AD-TDP type-α showed faster rates of hippocampal atrophy and smaller volumes of amygdala, temporal pole, and inferior temporal lobe compared to AD-TDP type-β.
- Pure-TDP was associated with slowest rates and less atrophy in all brain regions.
- The results suggest that there are differences and similarities in longitudinal brain volume loss between FTLD-TDP and non-FTLD TDP-43.
Study details
- Study designlongitudinal study
- Participants68
- Evidence strengthModerate
How this study scored 64/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 36 of the 56 points we could judge it on, which is 64 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (NeuroImage. Clinical) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| 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 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 68 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35168140) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 36 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 36 of the 56 points we could judge it on is 64 out of 100. |
| Total | 64 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Buciuc, M., Martin, P. R., Tosakulwong, N., Murray, M. E., Petrucelli, L., Senjem, M. L., et al. (2022). TDP-43-associated atrophy in brains with and without frontotemporal lobar degeneration. NeuroImage. Clinical. https://doi.org/10.1016/j.nicl.2022.102954
Vancouver
Buciuc M, Martin PR, Tosakulwong N, Murray ME, Petrucelli L, Senjem ML, et al. TDP-43-associated atrophy in brains with and without frontotemporal lobar degeneration. NeuroImage. Clinical. 2022. doi:10.1016/j.nicl.2022.102954. PMID: 35168140.
BibTeX
@article{buciuc2022-35168140,
author = {Buciuc, Marina and Martin, Peter R and Tosakulwong, Nirubol and Murray, Melissa E and Petrucelli, Leonard and Senjem, Matthew L and Spychalla, Anthony J and Knopman, David S and others},
title = {{TDP-43-associated atrophy in brains with and without frontotemporal lobar degeneration}},
journal = {NeuroImage. Clinical},
year = {2022},
doi = {10.1016/j.nicl.2022.102954},
pmid = {35168140},
url = {https://doi.org/10.1016/j.nicl.2022.102954}
}
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