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Structural and functional connectivity in tau mutation carriers: from presymptomatic to symptomatic frontotemporal dementia
Arabella Bouzigues, Vincent Le Du, Matthieu Joulot, Ninon Peysson, Marion Houot, Benoît Béranger, Lucy Louise Russell, Phoebe H. Foster et al.. Alzheimer s & Dementia, 2025-07-01
Topic: Brain proteins, microglia and lab models
Early isolated functional disruptions in salience/visual networks were present in asymptomatic carriers, along with anterior cingulate gray matter reductions. In prodromal carriers, functional changes extended to other networks, with additional structural damage in temporal poles/cingulate. This study shows that functional networks likely drive lifelong compensation for a genetically determined disease, manifesting clinically when structural damage reaches a critical threshold. This supports connectivity measures as potential biomarkers for MAPT-related neurodegeneration. HIGHLIGHTS: Our findings reveal the progressive and staged nature of structural and functional connectivity alterations in MAPT mutation carriers, with distinct patterns at each disease stage. In asymptomatic carriers, we identified early functional connectivity alterations in salience and visual networks, despite preserved white matter and only subtle gray matter atrophy. These appear to represent both response to pathology and possible compensatory mechanisms. In prodromal carriers, functional connectivity alterations were accompanied by structural damage, including cortical atrophy and white matter tract disruptions, in regions directly connected to early-affected networks. The sequential progression, from functional connectivity changes to structural degeneration, aligns with the hypothesis that tau propagates along axonal connections, disrupting neural network integrity before measurable atrophy occurs. We propose a theoretical data-driven model of biomarker evolution in MAPT mutation carriers, highlighting functional disruptions as early indicators and structural damage as a later-stage hallmark. These connectivity biomarkers have the potential to inform therapeutic strategies and clinical trial design.
Key findings
- Early isolated functional disruptions in salience/visual networks were present in asymptomatic carriers, along with anterior cingulate gray matter reductions.
- In prodromal carriers, functional changes extended to other networks, with additional structural damage in temporal poles/cingulate.
- This study shows that functional networks likely drive lifelong compensation for a genetically determined disease, manifesting clinically when structural damage reaches a critical threshold.
- This supports connectivity measures as potential biomarkers for MAPT-related neurodegeneration.
- HIGHLIGHTS: Our findings reveal the progressive and staged nature of structural and functional connectivity alterations in MAPT mutation carriers, with distinct patterns at each disease stage.
Why it matters
In people carrying MAPT mutations, functional connectivity changes appeared in asymptomatic carriers before structural damage, and later stages showed additional structural damage. The authors suggest connectivity measures could serve as biomarkers, but this is about tracking disease, not treating or preventing it.
Study details
- Evidence strengthLow
How this study scored 44/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 42 of the 96 points we could judge it on, which is 44 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 4 / 5 | 2025 — within 3 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 | 2 / 7 | Cited 9 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 5.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 56 institution(s) in 10 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40673371) |
| Free to read | 2 / 2 | Free to read |
| Points | 42 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 42 of the 96 points we could judge it on is 44 out of 100. |
| Total | 44 / 100 | — |
What each of these 20 components measures, and what this score is not →
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
Bouzigues, A., Le Du, V., Joulot, M., Peysson, N., Houot, M., Béranger, B., et al. (2025). Structural and functional connectivity in tau mutation carriers: from presymptomatic to symptomatic frontotemporal dementia. Alzheimer s & Dementia. https://doi.org/10.1002/alz.70367
Vancouver
Bouzigues A, Le Du V, Joulot M, Peysson N, Houot M, Béranger B, et al. Structural and functional connectivity in tau mutation carriers: from presymptomatic to symptomatic frontotemporal dementia. Alzheimer s & Dementia. 2025. doi:10.1002/alz.70367. PMID: 40673371.
BibTeX
@article{bouzigues2025-40673371,
author = {Bouzigues, Arabella and Le Du, Vincent and Joulot, Matthieu and Peysson, Ninon and Houot, Marion and Béranger, Benoît and Russell, Lucy Louise and Foster, Phoebe H. and others},
title = {{Structural and functional connectivity in tau mutation carriers: from presymptomatic to symptomatic frontotemporal dementia}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz.70367},
pmid = {40673371},
url = {https://doi.org/10.1002/alz.70367}
}
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