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Deconstructing pathological tau by biological process in early stages of Alzheimer disease: a method for quantifying tau spatial spread in neuroimaging
Doering S, McCullough A, Gordon BA, Chen CD, McKay N, Hobbs D, Keefe S, Flores S et al.. EBioMedicine, 2024-03-28
Topic: Amyloid, tau and blood-test diagnosis
Background Neuroimaging studies often quantify tau burden in standardized brain regions to assess Alzheimer disease (AD) progression. However, this method ignores another key biological process in which tau spreads to additional brain regions. We have developed a metric for calculating the extent tau pathology has spread throughout the brain and evaluate the relationship between this metric and tau burden across early stages of AD. Methods 445 cross-sectional participants (aged ≥ 50) who had MRI, amyloid PET, tau PET, and clinical testing were separated into disease-stage groups based on amyloid positivity and cognitive status (older cognitively normal control, preclinical AD, and symptomatic AD). Tau burden and tau spatial spread were calculated for all participants. Findings We found both tau metrics significantly elevated across increasing disease stages (p Interpretation Tau burden and tau spatial spread are both strong biomarkers for early AD but provide unique information, particularly at the preclinical stage. Tau spatial spread may demonstrate earlier changes than tau burden which could have broad impact in clinical trial design. Funding This research was supported by the Knight Alzheimer Disease Research Center (Knight ADRC, NIH grants P30AG066444, P01AG026276, P01AG003991), Dominantly Inherited Alzheimer Network (DIAN, NIH grants U01AG042791, U19AG03243808, R01AG052550-01A1, R01AG05255003), and the Barnes-Jewish Hospital Foundation Willman Scholar Fund.
Key findings
- Findings We found both tau metrics significantly elevated across increasing disease stages (p Interpretation Tau burden and tau spatial spread are both strong biomarkers for early AD but provide unique information, particularly at the preclinical stage.
Why it matters
In 445 participants across early Alzheimer's disease stages, both tau burden and a new measure of tau spatial spread were elevated with disease stage, and tau spatial spread may change earlier than tau burden. This is a cross-sectional imaging biomarker study and does not test any treatment, cure or prevention.
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Study details
- Study designcross-sectional
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (EBioMedicine) |
| Journal's citation record | 2 / 4 | EBioMedicine: journal h-index 181 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 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 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 | 3 / 6 | Cited 3.8× 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 | 2 / 4 | Last-listed author Sarah Keefe: h-index 22 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38552342) |
| Free to read | 2 / 2 | Free to read |
| Total | 45 / 100 | — |
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Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Doering, S., McCullough, A., Gordon, B. A., Chen, C. D., McKay, N., Hobbs, D., et al. (2024). Deconstructing pathological tau by biological process in early stages of Alzheimer disease: a method for quantifying tau spatial spread in neuroimaging. EBioMedicine. https://doi.org/10.1016/j.ebiom.2024.105080
Vancouver
Doering S, McCullough A, Gordon BA, Chen CD, McKay N, Hobbs D, et al. Deconstructing pathological tau by biological process in early stages of Alzheimer disease: a method for quantifying tau spatial spread in neuroimaging. EBioMedicine. 2024. doi:10.1016/j.ebiom.2024.105080. PMID: 38552342.
BibTeX
@article{doering2024-38552342,
author = {Doering, S. and McCullough, A. and Gordon, B. A. and Chen, C. D. and McKay, N. and Hobbs, D. and Keefe, S. and Flores, S. and others},
title = {{Deconstructing pathological tau by biological process in early stages of Alzheimer disease: a method for quantifying tau spatial spread in neuroimaging}},
journal = {EBioMedicine},
year = {2024},
doi = {10.1016/j.ebiom.2024.105080},
pmid = {38552342},
url = {https://doi.org/10.1016/j.ebiom.2024.105080}
}
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