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A biphasic astrocytic PTGDS trajectory marks a metabolic vulnerability stage in prodromal Alzheimer’s disease
Kim Y, Heo W, Park SJ, Kim Y, Cho YE, Lee Y, Kim J.. Research Square, 2026-08-27
Topic: Plasma and spinal-fluid biomarkers
PTGDS followed a biphasic astrocytic trajectory with a statistically resolved donor-level inflection (quadratic term −2.27, p = 0.006; vertex at pseudo-progression score 0.47, bootstrap 95% confidence interval 0.32 to 0.53). The same directional change was reproduced in ROSMAP and Banner brain proteomics (Alzheimer's disease versus control p = 3.4 × 10−3), and the biphasic pattern reconciles previously conflicting cerebrospinal fluid reports as stage-dependent. In cerebrospinal fluid, downstream neurofilament light tracked cognitive decline strongly and lipocalin-2 weakly, whereas PTGDS itself was tissue-restricted and not a stand-alone predictor. Limitations: The atlas provides pseudo-time rather than longitudinal sampling, so causality is not established. Coverage is restricted to one cortical region, donor coverage across the pseudo-progression range is uneven with a single donor in the lowest bin, lipocalin-2 transcript detection was sparse, zebrafish validation covered only the early compensatory phase, and the pharmacological arm was not tested after the inflection. These data position astrocytic PTGDS as a candidate stage marker, not a causal driver, of the compensatory-to-vulnerable shift in prodromal Alzheimer's disease, with potential relevance to stage-stratified patient selection. We propose, but do not establish, that attenuation of PTGDS after the inflection accompanies lipocalin-2-linked inflammation and suppression of nerve growth factor receptor.
Key findings
- PTGDS followed a biphasic astrocytic trajectory with a statistically resolved donor-level inflection (quadratic term −2.27, p = 0.006; vertex at pseudo-progression score 0.47, bootstrap 95% confidence interval 0.32 to 0.53).
- The same directional change was reproduced in ROSMAP and Banner brain proteomics (Alzheimer's disease versus control p = 3.4 × 10−3), and the biphasic pattern reconciles previously conflicting cerebrospinal fluid reports as stage-dependent.
- In cerebrospinal fluid, downstream neurofilament light tracked cognitive decline strongly and lipocalin-2 weakly, whereas PTGDS itself was tissue-restricted and not a stand-alone predictor.
- Limitations: The atlas provides pseudo-time rather than longitudinal sampling, so causality is not established.
- Coverage is restricted to one cortical region, donor coverage across the pseudo-progression range is uneven with a single donor in the lowest bin, lipocalin-2 transcript detection was sparse, zebrafish validation covered only the early compensatory phase, and the pharmacological arm was not tested after the inflection.
Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 35 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for 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 22 of the 62 points we could judge it on, which is 35 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 | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 | 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 | 22 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 22 of the 62 points we could judge it on is 35 out of 100. |
| Total | 35 / 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. Check the citation against the original before you use it.
APA 7th
Kim, Y., Heo, W., Park, S. J., Cho, Y. E., Lee, Y., & Kim, J. (2026). A biphasic astrocytic PTGDS trajectory marks a metabolic vulnerability stage in prodromal Alzheimer’s disease. Research Square. https://doi.org/10.21203/rs.3.rs-9499795/v3
Vancouver
Kim Y, Heo W, Park SJ, Cho YE, Lee Y, Kim J. A biphasic astrocytic PTGDS trajectory marks a metabolic vulnerability stage in prodromal Alzheimer’s disease. Research Square. 2026. doi:10.21203/rs.3.rs-9499795/v3.
BibTeX
@article{kim2026-cbfae738,
author = {Kim, Y. and Heo, W. and Park, S. J. and Cho, Y. E. and Lee, Y. and Kim, J.},
title = {{A biphasic astrocytic PTGDS trajectory marks a metabolic vulnerability stage in prodromal Alzheimer’s disease}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-9499795/v3},
url = {https://doi.org/10.21203/rs.3.rs-9499795/v3}
}
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