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Patient‐derived forebrain cortical organoids reveal biphasic tau–MAP6–microtubule axis dysfunction in tauopathy
Xiaohuan Sun, Skandha Ramakrishnan, Victor C. Ogbolu, Nicholas M. Kanaan, Celeste M M. Karch, Peter W. Baas, Qiang Liang. Alzheimer s & Dementia, 2026-07-01
Topic: Brain proteins, microglia and lab models
Early-phase tau mutant organoids showed elevated tau, hyperdynamic microtubules, and neuronal hyperexcitability, partially reversible by tau reduction. Late-phase organoids exhibited insoluble tau accumulation, microtubule hyperstability, and neurodegeneration and reactive astrocytes, accompanied by opposing, phase-dependent MAP6 changes. This work reveals a biphasic tau-MAP6-microtubule mechanism driving tauopathy and establishes these organoids as a platform for phase-specific therapy.
Key findings
- Early-phase tau mutant organoids showed elevated tau, hyperdynamic microtubules, and neuronal hyperexcitability, partially reversible by tau reduction.
- Late-phase organoids exhibited insoluble tau accumulation, microtubule hyperstability, and neurodegeneration and reactive astrocytes, accompanied by opposing, phase-dependent MAP6 changes.
- This work reveals a biphasic tau-MAP6-microtubule mechanism driving tauopathy and establishes these organoids as a platform for phase-specific therapy.
Why it matters
In patient-derived brain organoids, early-phase tau mutant tissue showed elevated tau and hyperdynamic microtubules that were partially reversible by tau reduction, while late-phase tissue showed insoluble tau, microtubule hyperstability and neurodegeneration. This is laboratory research using organoids and does not test a treatment in people.
Study details
- Evidence strengthLow
How this study scored 34/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 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 | Laboratory or animal study (title names “organoids”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 0 / 6 | Cited 0.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Qiang Liang: h-index 24 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42411568) |
| Free to read | 2 / 2 | Free to read |
| Total | 34 / 100 | — |
What each of these 20 components measures, and what this score is not →
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Sun, X., Ramakrishnan, S., Ogbolu, V. C., Kanaan, N. M., Karch, C. M. M., Baas, P. W., et al. (2026). Patient‐derived forebrain cortical organoids reveal biphasic tau–MAP6–microtubule axis dysfunction in tauopathy. Alzheimer s & Dementia. https://doi.org/10.1002/alz.71565
Vancouver
Sun X, Ramakrishnan S, Ogbolu VC, Kanaan NM, Karch CMM, Baas PW, et al. Patient‐derived forebrain cortical organoids reveal biphasic tau–MAP6–microtubule axis dysfunction in tauopathy. Alzheimer s & Dementia. 2026. doi:10.1002/alz.71565. PMID: 42411568.
BibTeX
@article{sun2026-42411568,
author = {Sun, Xiaohuan and Ramakrishnan, Skandha and Ogbolu, Victor C. and Kanaan, Nicholas M. and Karch, Celeste M M. and Baas, Peter W. and Liang, Qiang},
title = {{Patient‐derived forebrain cortical organoids reveal biphasic tau–MAP6–microtubule axis dysfunction in tauopathy}},
journal = {Alzheimer s \& Dementia},
year = {2026},
doi = {10.1002/alz.71565},
pmid = {42411568},
url = {https://doi.org/10.1002/alz.71565}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.