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MRI measures of cortical microstructural damage associate with tau accumulation in presymptomatic Alzheimer’s disease
Weston PS, Coath W, Brown T, Scott CJ, Malone IB, Årstad E, Awais R, Sander K et al.. medRxiv, 2025-12-16
Topic: Plasma and spinal-fluid biomarkers
Objectives Amyloid lowering therapies for Alzheimer’s disease are most effective in those without significant neocortical tau spread. Currently, the only method for anatomically staging tau is through PET scanning, which is largely unavailable in clinical settings. We assessed whether advanced MRI biomarkers of cortical microstructure may provide a more accessible option for assessing early neocortical tau accumulation. Methods 217 asymptomatic individuals underwent amyloid-β PET, tau PET and multi-shell diffusion 3T MRI. Neurite orientation dispersion and density imaging (NODDI) metrics including orientation dispersion index (ODI; a proxy measure of dendritic complexity), and free water fraction (FWF) were calculated. Analysis focused on a meta-temporal cortical composite region, the first site of neocortical tau beyond the medial temporal lobe (MTL). Results Meta-temporal tau burden was associated with meta-temporal ODI (Pearson’s r=-0.24, p=0.001), with a weaker association also seen with meta-temporal FWF (r=-0.14, p=0.07). Within the amyloid-β positive group, ODI discriminated between those with and without meta-temporal tau positivity (area under the curve=0.86). Discussion NODDI-derived ODI is associated with tau PET signal, even in preclinical disease and may discriminate individuals with-and without tau beyond the MTL. NODDI represents a potential alternative imaging tool for staging tau spread, aiding future treatment stratification and delivery.
Key findings
- Objectives Amyloid lowering therapies for Alzheimer’s disease are most effective in those without significant neocortical tau spread.
- Results Meta-temporal tau burden was associated with meta-temporal ODI (Pearson’s r=-0.24, p=0.001), with a weaker association also seen with meta-temporal FWF (r=-0.14, p=0.07).
- Discussion NODDI-derived ODI is associated with tau PET signal, even in preclinical disease and may discriminate individuals with-and without tau beyond the MTL.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 19 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. 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 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 and multi-centre collaboration, so those were left out: it earned 12 of the 62 points we could judge it on, which is 19 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 | — / 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 12 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 12 of the 62 points we could judge it on is 19 out of 100. |
| Total | 19 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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
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
Weston, P. S., Coath, W., Brown, T., Scott, C. J., Malone, I. B., Årstad, E., et al. (2025). MRI measures of cortical microstructural damage associate with tau accumulation in presymptomatic Alzheimer’s disease. medRxiv. https://doi.org/10.64898/2025.12.15.25340517
Vancouver
Weston PS, Coath W, Brown T, Scott CJ, Malone IB, Årstad E, et al. MRI measures of cortical microstructural damage associate with tau accumulation in presymptomatic Alzheimer’s disease. medRxiv. 2025. doi:10.64898/2025.12.15.25340517.
BibTeX
@article{weston2025-d166a8a7,
author = {Weston, P. S. and Coath, W. and Brown, T. and Scott, C. J. and Malone, I. B. and Årstad, E. and Awais, R. and Sander, K. and others},
title = {{MRI measures of cortical microstructural damage associate with tau accumulation in presymptomatic Alzheimer’s disease}},
journal = {medRxiv},
year = {2025},
doi = {10.64898/2025.12.15.25340517},
url = {https://doi.org/10.64898/2025.12.15.25340517}
}
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