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Basal Ganglia Iron Accumulation Mediates Stage-Dependent Associations Between Plasma pTau217 and Hippocampal Atrophy in Alzheimer’s Disease
Gao P, Tan H, Li G, Liang J, Yang M, Xu D, Wang Q, Liang S et al.. Research Square, 2026-10-19
Topic: Plasma and spinal-fluid biomarkers
Background Plasma phosphorylated tau 217 (pTau217) reflects cerebral tau pathology in Alzheimer's disease (AD), yet how brain iron deposition mediates the relationship between pTau217 and hippocampal atrophy across AD stages remains unknown. Methods 193 participants were classified as AD (n = 94) or Non-AD (n = 99) based on a plasma pTau217 threshold of 0.242 pg/mL, and AD individuals were further staged as preclinical AD, prodromal AD, or AD dementia. All underwent plasma biomarker profiling, quantitative susceptibility mapping (QSM), structural MRI, and neuropsychological assessment. Stage-dependent, iron-stratified, and mediation and cutoff-sensitivity analyses were performed. Results AD individuals showed increased iron deposition in the basal ganglia, predominantly the putamen, and reduced bilateral hippocampal volumes. Basal ganglia iron correlated positively with pTau217 and inversely with global cognition, episodic memory, language, and visuospatial function (all pFDR < 0.05). Iron–hippocampus associations strengthened progressively across the continuum, peaked in prodromal AD, and plateaued in dementia, and iron burden modified the pTau217–hippocampus slope. Basal ganglia iron partially mediated the pTau217–hippocampal volume relationship bilaterally (both p < 0.05), accounting for 6.4% to 7.9% of the total effect. Conclusion Basal ganglia iron serves as a stage-dependent mediator linking pTau217 to hippocampal neurodegeneration, with prodromal AD potentially indicating a particularly vulnerable stage for iron-targeted interventions and iron profiling for patient stratification.
Key findings
- Results AD individuals showed increased iron deposition in the basal ganglia, predominantly the putamen, and reduced bilateral hippocampal volumes.
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Study details
- Participants94
- Effect sizeor 6.4; 7.9%
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 31 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design 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 19 of the 62 points we could judge it on, which is 31 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| 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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 1 / 4 | 94 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 | — / 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 | 19 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 19 of the 62 points we could judge it on is 31 out of 100. |
| Total | 31 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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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
Gao, P., Tan, H., Li, G., Liang, J., Yang, M., Xu, D., et al. (2026). Basal Ganglia Iron Accumulation Mediates Stage-Dependent Associations Between Plasma pTau217 and Hippocampal Atrophy in Alzheimer’s Disease. Research Square. https://doi.org/10.21203/rs.3.rs-11017150/v1
Vancouver
Gao P, Tan H, Li G, Liang J, Yang M, Xu D, et al. Basal Ganglia Iron Accumulation Mediates Stage-Dependent Associations Between Plasma pTau217 and Hippocampal Atrophy in Alzheimer’s Disease. Research Square. 2026. doi:10.21203/rs.3.rs-11017150/v1.
BibTeX
@article{gao2026-cac95d7a,
author = {Gao, P. and Tan, H. and Li, G. and Liang, J. and Yang, M. and Xu, D. and Wang, Q. and Liang, S. and others},
title = {{Basal Ganglia Iron Accumulation Mediates Stage-Dependent Associations Between Plasma pTau217 and Hippocampal Atrophy in Alzheimer’s Disease}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-11017150/v1},
url = {https://doi.org/10.21203/rs.3.rs-11017150/v1}
}
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