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Serum GFAP levels correlate with astrocyte reactivity, post-mortem brain atrophy and neurofibrillary tangles
Sánchez-Juan P, Valeriano-Lorenzo E, Ruiz-González A, Pastor AB, Rodrigo Lara H, López-González F, Zea-Sevilla MA, Valentí M, Frades B, Ruiz P, Saiz L, Burgueño-García I, et al.. Brain, 2024-05-03
Topic: Brain proteins, microglia and lab models
The main findings demonstrated an association between serum GFAP level and post-mortem tau pathology (β = 12.85; P < 0.001) that was independent of amyloid deposits (β = 13.23; P = 0.02). Independently of Alzheimer's disease, serum GFAP levels were shown to be associated with two other pathologies targeting the temporal lobes-hippocampal sclerosis (β = 3.64; P = 0.03) and argyrophilic grain disease (β = -6.11; P = 0.02). Finally, serum GFAP levels were revealed to be correlated with astrocyte reactivity, using the brain GFAP-immunostained area as a proxy (ρ = 0.21; P = 0.02). Our results contribute to increasing evidence suggesting a role for blood GFAP as an Alzheimer's disease biomarker, and the findings offer mechanistic insights into the relationship between blood GFAP and Alzheimer's disease neuropathology, highlighting its ties with tau burden. Moreover, the data highlighting an independent association between serum GFAP levels and other neuropathological lesions provide information for clinicians to consider when interpreting test results. The longitudinal design and correlation with post-mortem data reinforce the robustness of our findings. However, studies correlating blood biomarkers and neuropathological assessments are still scant, and further research is needed to replicate and validate these results in diverse populations.
Key findings
- The main findings demonstrated an association between serum GFAP level and post-mortem tau pathology (β = 12.85; P < 0.001) that was independent of amyloid deposits (β = 13.23; P = 0.02).
- Independently of Alzheimer's disease, serum GFAP levels were shown to be associated with two other pathologies targeting the temporal lobes-hippocampal sclerosis (β = 3.64; P = 0.03) and argyrophilic grain disease (β = -6.11; P = 0.02).
- Finally, serum GFAP levels were revealed to be correlated with astrocyte reactivity, using the brain GFAP-immunostained area as a proxy (ρ = 0.21; P = 0.02).
- Our results contribute to increasing evidence suggesting a role for blood GFAP as an Alzheimer's disease biomarker, and the findings offer mechanistic insights into the relationship between blood GFAP and Alzheimer's disease neuropathology, highlighting its ties with tau burden.
- Moreover, the data highlighting an independent association between serum GFAP levels and other neuropathological lesions provide information for clinicians to consider when interpreting test results.
Why it matters
This cohort study found that serum GFAP levels were associated with post-mortem tau pathology independently of amyloid deposits, and were also associated with hippocampal sclerosis and argyrophilic grain disease. The authors state that further research is needed to replicate and validate these results in diverse populations, so this is biomarker and mechanistic evidence rather than a treatment or cure.
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Study details
- Study designcohort
- Participants139
- Effect sizeAUC 0.91 for autopsy-confirmed AD vs non-AD dementia; β = 12.85 for association with tau pathology
- Evidence strengthModerate
Limitations
Cohort was predominantly AD dementia and female, representative of institutionalised older people but limiting generalisation; lack of major neurovascular pathology may explain the absence of a GFAP-vascular association; late-stage dementia sample limits conclusions about diagnostic accuracy in earlier stages or screening.
How this study scored 71/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 70 of the 98 points we could judge it on, which is 71 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 139 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 4 / 7 | Cited 89 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.2 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 5 / 6 | Cited 24.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 3 / 4 | Cited 89 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Alberto Rábano: h-index 53 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Instituto de Salud Carlos III: institution h-index 649 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38634687) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 70 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 70 of the 98 points we could judge it on is 71 out of 100. |
| Total | 71 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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
Sánchez-Juan, P., Valeriano-Lorenzo, E., Ruiz-González, A., Pastor, A. B., Rodrigo Lara, H., López-González, F., et al. (2024). Serum GFAP levels correlate with astrocyte reactivity, post-mortem brain atrophy and neurofibrillary tangles. Brain. https://doi.org/10.1093/brain/awae035
Vancouver
Sánchez-Juan P, Valeriano-Lorenzo E, Ruiz-González A, Pastor AB, Rodrigo Lara H, López-González F, et al. Serum GFAP levels correlate with astrocyte reactivity, post-mortem brain atrophy and neurofibrillary tangles. Brain. 2024. doi:10.1093/brain/awae035. PMID: 38634687.
BibTeX
@article{sanchezjuan2024-38634687,
author = {Sánchez-Juan, P. and Valeriano-Lorenzo, E. and Ruiz-González, A. and Pastor, A. B. and Rodrigo Lara, H. and López-González, F. and Zea-Sevilla, M. A. and Valentí, M. and Frades, B. and Ruiz, P. and Saiz, L. and Burgueño-García, I. and others},
title = {{Serum GFAP levels correlate with astrocyte reactivity, post-mortem brain atrophy and neurofibrillary tangles}},
journal = {Brain},
year = {2024},
doi = {10.1093/brain/awae035},
pmid = {38634687},
url = {https://doi.org/10.1093/brain/awae035}
}
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