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A mass-producible macaque model displays a durable Alzheimer-like cognitive deficit and hallmark amyloid-β/tau/neurofilament light chain pathologies
He F, Shi WJ, Liu W, Fan JX, He ZG, Zhang YQ, Xiao J, Ruan WW et al.. Journal of Alzheimer's disease : JAD, 2025-04-23
Topic: Amyloid, tau and blood-test diagnosis
BackgroundAlzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by cognitive deficit and pathological accumulation of amyloid-β (Aβ) and tau proteins. The rodent models have contributed greatly to unravel AD pathogenesis, but these AD models have been shown a modest clinical translational effectiveness.ObjectiveTherefore, developing mass-producible primate AD models is promising for more effective drug development.MethodsHere, we constructed the AD monkey models by simultaneously infusing AAV-Tau and Aβ into different brain regions.ResultsThe induced monkeys showed a durable cognitive impairment lasting for at least 10 months after the modeling. Simultaneously, the increased levels of total tau and hyperphosphorylated tau (pTau) at several AD-associated sites, and neurofilament light chains (NfL) with altered Aβ level were detected at different time poin
Key findings
- The rodent models have contributed greatly to unravel AD pathogenesis, but these AD models have been shown a modest clinical translational effectiveness.ObjectiveTherefore, developing mass-producible primate AD models is promising for more effective drug development.MethodsHere, we constructed the AD monkey models by simultaneously infusing AAV-Tau and Aβ into different brain regions.ResultsThe induced monkeys showed a durable cognitive impairment lasting for at least 10 months after the modeling.
- Simultaneously, the increased levels of total tau and hyperphosphorylated tau (pTau) at several AD-associated sites, and neurofilament light chains (NfL) with altered Aβ level were detected at different time points in cerebrospinal fluid and/or plasma by using MSD kits.
- The increased brain accumulation of Aβ and tau proteins was also detected by positron emission tomography/magnetic resonance imaging and immunohistochemical staining.
- The model monkeys also had significant glial activation; an indicator of inflammation commonly seen in the brains of AD patients.ConclusionsTogether, this study provides mass-producible monkey models showing durable AD-like hallmark pathologies (Aβ, tau, NfL, i.e., ATN) and cognitive deficits.
Why it matters
This study created macaque models by infusing AAV-Tau and Aβ into brain regions, producing a cognitive deficit lasting at least 10 months with tau, pTau, NfL and Aβ changes. It is an animal model intended for drug development and does not itself treat, cure or prevent Alzheimer's disease in people.
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Study details
- Evidence strengthLow
How this study scored 36/100
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 (Journal of Alzheimer's disease : JAD) |
| Journal's citation record | 2 / 4 | Journal of Alzheimer s Disease: journal h-index 218 (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 | 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 | Laboratory or animal study (title names “macaque”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.6× 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 | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jian‐Zhi Wang: h-index 27 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Huazhong University of Science and Technology: institution h-index 934 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40267273) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 36 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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
He, F., Shi, W. J., Liu, W., Fan, J. X., He, Z. G., Zhang, Y. Q., et al. (2025). A mass-producible macaque model displays a durable Alzheimer-like cognitive deficit and hallmark amyloid-β/tau/neurofilament light chain pathologies. Journal of Alzheimer's disease : JAD. https://doi.org/10.1177/13872877251334316
Vancouver
He F, Shi WJ, Liu W, Fan JX, He ZG, Zhang YQ, et al. A mass-producible macaque model displays a durable Alzheimer-like cognitive deficit and hallmark amyloid-β/tau/neurofilament light chain pathologies. Journal of Alzheimer's disease : JAD. 2025. doi:10.1177/13872877251334316. PMID: 40267273.
BibTeX
@article{he2025-40267273,
author = {He, F. and Shi, W. J. and Liu, W. and Fan, J. X. and He, Z. G. and Zhang, Y. Q. and Xiao, J. and Ruan, W. W. and others},
title = {{A mass-producible macaque model displays a durable Alzheimer-like cognitive deficit and hallmark amyloid-β/tau/neurofilament light chain pathologies}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2025},
doi = {10.1177/13872877251334316},
pmid = {40267273},
url = {https://doi.org/10.1177/13872877251334316}
}
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