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Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer's disease
Bellaver B, Povala G, Ferreira PCL, Ferrari-Souza JP, Leffa DT, Lussier FZ, Benedet AL, Ashton NJ, Triana-Baltzer G, Kolb HC, Tissot C, Therriault J, et al.. Nature Medicine, 2023-05-29
Topic: Amyloid, tau and blood-test diagnosis
An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aβ effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts (n = 1,016), we tested whether astrocyte reactivity modulates the association of Aβ with tau phosphorylation in CU individuals. We found that Aβ was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast + ). Cross-sectional and longitudinal tau-positron emission tomography analyses revealed an AD-like pattern of tau tangle accumulation as a function of Aβ only in CU Ast + individuals. Our findings suggest astrocyte reactivity as an important upstream event linking Aβ with initial tau pathology, which may have implications for the biological definition of preclinical AD and for selecting CU individuals for clinical trials.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Bellaver, B., Povala, G., Ferreira, P. C. L., Ferrari-Souza, J. P., Leffa, D. T., Lussier, F. Z., et al. (2023). Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer's disease. Nature Medicine. https://doi.org/10.1038/s41591-023-02380-x
Vancouver
Bellaver B, Povala G, Ferreira PCL, Ferrari-Souza JP, Leffa DT, Lussier FZ, et al. Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer's disease. Nature Medicine. 2023. doi:10.1038/s41591-023-02380-x. PMID: 37248300.
BibTeX
@article{bellaver2023-37248300,
author = {Bellaver, B. and Povala, G. and Ferreira, P. C. L. and Ferrari-Souza, J. P. and Leffa, D. T. and Lussier, F. Z. and Benedet, A. L. and Ashton, N. J. and Triana-Baltzer, G. and Kolb, H. C. and Tissot, C. and Therriault, J. and others},
title = {{Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer's disease}},
journal = {Nature Medicine},
year = {2023},
doi = {10.1038/s41591-023-02380-x},
pmid = {37248300},
url = {https://doi.org/10.1038/s41591-023-02380-x}
}
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.
Key findings
- An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration.
- In vitro evidence suggests that reactive astrocytes unleash Aβ effects in pathological tau phosphorylation.
- We found that Aβ was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast + ).
- Cross-sectional and longitudinal tau-positron emission tomography analyses revealed an AD-like pattern of tau tangle accumulation as a function of Aβ only in CU Ast + individuals.
- Our findings suggest astrocyte reactivity as an important upstream event linking Aβ with initial tau pathology, which may have implications for the biological definition of preclinical AD and for selecting CU individuals for clinical trials.
Why it matters
In three cohorts totalling 1,016 cognitively unimpaired individuals, amyloid-beta was associated with increased plasma phosphorylated tau and an Alzheimer's-like pattern of tau accumulation only in people positive for astrocyte reactivity. The findings suggest astrocyte reactivity as an upstream event linking amyloid-beta with initial tau pathology and may help select participants for trials, but no treatment is tested.
Study details
- Study designcohort
- Participants1,016
- Evidence strengthModerate
Limitations
The longitudinal tau-PET analysis had a relatively small sample so replication is highly desirable; dichotomised biomarker cut-offs are subject to analytical idiosyncrasies and may change with method; and the cohorts were mainly White participants, limiting generalisability.
How this study scored 80/100
Published in a top-tier journal, and it is a cohort study following people over time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 78 of the 98 points we could judge it on, which is 80 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature Medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,016 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 | 6 / 7 | Cited 316 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 63.2 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 6 / 6 | Cited 46.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 38 other studies in this library |
| Still being cited | 4 / 4 | Cited 290 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Tharick Ali Pascoal: h-index 61 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 18 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37248300) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 78 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 78 of the 98 points we could judge it on is 80 out of 100. |
| Total | 80 / 100 | — |
What each of these 20 components measures, and what this score is not →
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