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Combined Connectomics, MAPT Gene Expression, and Amyloid Deposition to Explain Regional Tau Deposition in Alzheimer Disease
Zheng L, Rubinski A, Denecke J, Luan Y, Smith R, Strandberg O, Stomrud E, Ossenkoppele R et al.. Annals of neurology, 2023-10-25
Topic: Brain proteins, microglia and lab models
Objective We aimed to test whether region-specific factors, including spatial expression patterns of the tau-encoding gene MAPT and regional levels of amyloid positron emission tomography (PET), enhance connectivity-based modeling of the spatial variability in tau-PET deposition in the Alzheimer disease (AD) spectrum. Methods We included 685 participants (395 amyloid-positive participants within AD spectrum and 290 amyloid-negative controls) with tau-PET and amyloid-PET from 3 studies (Alzheimer's Disease Neuroimaging Initiative, 18 F-AV-1451-A05, and BioFINDER-1). Resting-state functional magnetic resonance imaging was obtained in healthy controls (n = 1,000) from the Human Connectome Project, and MAPT gene expression from the Allen Human Brain Atlas. Based on a brain-parcellation atlas superimposed onto all modalities, we obtained region of interest (ROI)-to-ROI functional connectivity, ROI-level PET values, and MAPT gene expression. In stepwise regression analyses, we tested connectivity, MAPT gene expression, and amyloid-PET as predictors of group-averaged and individual tau-PET ROI values in amyloid-positive participants. Results Connectivity alone explained 21.8 to 39.2% (range across 3 studies) of the variance in tau-PET ROI values averaged across amyloid-positive participants. Stepwise addition of MAPT gene expression and amyloid-PET increased the proportion of explained variance to 30.2 to 46.0% and 45.0 to 49.9%, respectively. Similarly, for the prediction of patient-level tau-PET ROI values, combining all 3 predictors significantly improved the variability explained (mean adjusted R 2 range across studies = 0.118-0.148, 0.156-0.196, and 0.251-0.333 for connectivity alone, connectivity plus MAPT expression, and all 3 modalities combined, respectively). Interpretation Across 3 study samples, combining the functional connectome and molecular properties substantially enhanced the explanatory power compared to single modalities, providing a valuable tool to explain regional susceptibility to tau deposition in AD. ANN NEUROL 2024;95:274-287.
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APA 7th
Zheng, L., Rubinski, A., Denecke, J., Luan, Y., Smith, R., Strandberg, O., et al. (2024). Combined Connectomics, MAPT Gene Expression, and Amyloid Deposition to Explain Regional Tau Deposition in Alzheimer Disease. Annals of neurology. https://doi.org/10.1002/ana.26818
Vancouver
Zheng L, Rubinski A, Denecke J, Luan Y, Smith R, Strandberg O, et al. Combined Connectomics, MAPT Gene Expression, and Amyloid Deposition to Explain Regional Tau Deposition in Alzheimer Disease. Annals of neurology. 2024. doi:10.1002/ana.26818. PMID: 37837382.
BibTeX
@article{zheng2024-37837382,
author = {Zheng, L. and Rubinski, A. and Denecke, J. and Luan, Y. and Smith, R. and Strandberg, O. and Stomrud, E. and Ossenkoppele, R. and others},
title = {{Combined Connectomics, MAPT Gene Expression, and Amyloid Deposition to Explain Regional Tau Deposition in Alzheimer Disease}},
journal = {Annals of neurology},
year = {2024},
doi = {10.1002/ana.26818},
pmid = {37837382},
url = {https://doi.org/10.1002/ana.26818}
}
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Key findings
- Results Connectivity alone explained 21.8 to 39.2% (range across 3 studies) of the variance in tau-PET ROI values averaged across amyloid-positive participants.
- Similarly, for the prediction of patient-level tau-PET ROI values, combining all 3 predictors significantly improved the variability explained (mean adjusted R 2 range across studies = 0.118-0.148, 0.156-0.196, and 0.251-0.333 for connectivity alone, connectivity plus MAPT expression, and all 3 modalities combined, respectively).
- Interpretation Across 3 study samples, combining the functional connectome and molecular properties substantially enhanced the explanatory power compared to single modalities, providing a valuable tool to explain regional susceptibility to tau deposition in AD.
Why it matters
Across three studies, combining brain connectivity, MAPT gene expression, and amyloid PET explained more of the regional pattern of tau deposition in Alzheimer's disease than connectivity alone. This improves understanding of how tau spreads in the brain but does not test treatment, cure, or prevention.
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Study details
- Participants1,000
- Effect size39.2%; 46.0%; 49.9%
- Evidence strengthLow
How this study scored 51/100
Published in a leading specialty journal. Scored zero for study design 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 49 of the 96 points we could judge it on, which is 51 out of 100.
| 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 | 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 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,000 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 2 / 7 | Cited 14 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.5 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 2 / 6 | Cited 2.5× 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 14 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 | 1 / 3 | Ludwig-Maximilians-Universität München: institution h-index 1,224 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 16 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37837382) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 49 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 49 of the 96 points we could judge it on is 51 out of 100. |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
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