Home › Research › Biomarkers
Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum
Benedet AL, Milà-Alomà M, Vrillon A, Ashton NJ, Pascoal TA, Lussier F, Karikari TK, Hourregue C et al.. JAMA neurology, 2021-12-01
Topic: Amyloid, tau and blood-test diagnosis
Objective To evaluate plasma GFAP levels throughout the entire AD continuum, from preclinical AD to AD dementia, compared with CSF GFAP. Results were confirmed in the Alzheimer's and Families (ALFA+) study (Barcelona, Spain), which included individuals with preclinical AD, and the BioCogBank Paris Lariboisière cohort (Paris, France), which included individuals with symptomatic AD. Results of amyloid positron emission tomography (PET) were available in TRIAD and ALFA+, and results of tau PET were available in TRIAD. Results A total of 300 TRIAD participants (177 women [59.0%]; mean [SD] age, 64.6 [17.6] years), 384 ALFA+ participants (234 women [60.9%]; mean [SD] age, 61.1 [4.7] years), and 187 BioCogBank Paris Lariboisière participants (116 women [62.0%]; mean [SD] age, 69.9 [9.2] years) were included. Plasma GFAP levels were significantly higher in individuals with preclinical AD in comparison with cognitively unimpaired (CU) Aβ-negative individuals (TRIAD: Aβ-negative mean [SD], 185.1 [93.5] pg/mL, Aβ-positive mean [SD], 285.0 [142.6] pg/mL; ALFA+: Aβ-negative mean [SD], 121.9 [42.4] pg/mL, Aβ-positive mean [SD], 169.9 [78.5] pg/mL). Moreover, plasma GFAP levels were positively associated with tau pathology only among individuals with concomitant Aβ pathology. Conclusions and relevance This study suggests that plasma GFAP is a sensitive biomarker for detecting and tracking reactive astrogliosis and Aβ pathology even among individuals in the early stages of AD.
Key findings
- Objective To evaluate plasma GFAP levels throughout the entire AD continuum, from preclinical AD to AD dementia, compared with CSF GFAP.
- Results were confirmed in the Alzheimer's and Families (ALFA+) study (Barcelona, Spain), which included individuals with preclinical AD, and the BioCogBank Paris Lariboisière cohort (Paris, France), which included individuals with symptomatic AD.
- Results of amyloid positron emission tomography (PET) were available in TRIAD and ALFA+, and results of tau PET were available in TRIAD.
- Results A total of 300 TRIAD participants (177 women [59.0%]; mean [SD] age, 64.6 [17.6] years), 384 ALFA+ participants (234 women [60.9%]; mean [SD] age, 61.1 [4.7] years), and 187 BioCogBank Paris Lariboisière participants (116 women [62.0%]; mean [SD] age, 69.9 [9.2] years) were included.
- Plasma GFAP levels were significantly higher in individuals with preclinical AD in comparison with cognitively unimpaired (CU) Aβ-negative individuals (TRIAD: Aβ-negative mean [SD], 185.1 [93.5] pg/mL, Aβ-positive mean [SD], 285.0 [142.6] pg/mL; ALFA+: Aβ-negative mean [SD], 121.9 [42.4] pg/mL, Aβ-positive mean [SD], 169.9 [78.5] pg/mL).
Why it matters
Plasma GFAP levels were higher in people with preclinical Alzheimer's disease than in cognitively unimpaired individuals without amyloid, and were linked to tau pathology only when amyloid pathology was also present. This points to plasma GFAP as a possible biomarker for detecting and tracking Alzheimer's disease, not as a treatment or cure.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designcross-sectional
- Participants300
- Effect size59.0%; 60.9%; 62.0%
- Evidence strengthModerate
How this study scored 75/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 72 of the 96 points we could judge it on, which is 75 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in 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 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 300 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 628 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 89.7 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 6 / 6 | Cited 53.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 67 other studies in this library |
| Still being cited | 4 / 4 | Cited 443 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Alyssa Stevensson holds only 1 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 28 institution(s) in 7 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34661615) |
| Free to read | 2 / 2 | Free to read |
| Points | 72 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 72 of the 96 points we could judge it on is 75 out of 100. |
| Total | 75 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamaneurol.2021.3671
- PubMed: 34661615
- Original source →
- Free full text: PubMed Central →
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
Benedet, A. L., Milà-Alomà, M., Vrillon, A., Ashton, N. J., Pascoal, T. A., Lussier, F., et al. (2021). Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum. JAMA neurology. https://doi.org/10.1001/jamaneurol.2021.3671
Vancouver
Benedet AL, Milà-Alomà M, Vrillon A, Ashton NJ, Pascoal TA, Lussier F, et al. Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum. JAMA neurology. 2021. doi:10.1001/jamaneurol.2021.3671. PMID: 34661615.
BibTeX
@article{benedet2021-34661615,
author = {Benedet, A. L. and Milà-Alomà, M. and Vrillon, A. and Ashton, N. J. and Pascoal, T. A. and Lussier, F. and Karikari, T. K. and Hourregue, C. and others},
title = {{Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum}},
journal = {JAMA neurology},
year = {2021},
doi = {10.1001/jamaneurol.2021.3671},
pmid = {34661615},
url = {https://doi.org/10.1001/jamaneurol.2021.3671}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 20.
Later studies that cite this one
67 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.