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Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer's disease
Chatterjee P, Pedrini S, Stoops E, Goozee K, Villemagne VL, Asih PR, Verberk IMW, Dave P et al.. Translational psychiatry, 2021-01-11
Topic: Plasma and spinal-fluid biomarkers
Glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, can be measured in blood samples, and has been associated with Alzheimer's disease (AD). However, plasma GFAP has not been investigated in cognitively normal older adults at risk of AD, based on brain amyloid-β (Aβ) load. Cross-sectional analyses were carried out for plasma GFAP and plasma Aβ1-42/Aβ1-40 ratio, a blood-based marker associated with brain Aβ load, in participants (65-90 years) categorised into low (Aβ-, n = 63) and high (Aβ+, n = 33) brain Aβ load groups via Aβ positron emission tomography. Plasma GFAP, Aβ1-42, and Aβ1-40 were measured using the Single molecule array (Simoa) platform. Plasma GFAP levels were significantly higher (p < 0.00001), and plasma Aβ1-42/Aβ1-40 ratios were significantly lower (p < 0.005), in Aβ+ participants compared to Aβ- participants, adjusted for covariates age, sex, and apolipoprotein E-ε4 carriage. A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished Aβ+ from Aβ- (area under the curve, AUC = 0.78), but was outperformed when plasma GFAP was added to the base model (AUC = 0.91) and further improved with plasma Aβ1-42/Aβ1-40 ratio (AUC = 0.92). The current findings demonstrate that plasma GFAP levels are elevated in cognitively normal older adults at risk of AD. These observations suggest that astrocytic damage or activation begins from the pre-symptomatic stage of AD and is associated with brain Aβ load. Observations from the present study highlight the potential of plasma GFAP to contribute to a diagnostic blood biomarker panel (along with plasma Aβ1-42/Aβ1-40 ratios) for cognitively normal older adults at risk of AD.
Key findings
- Glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, can be measured in blood samples, and has been associated with Alzheimer's disease (AD).
- Cross-sectional analyses were carried out for plasma GFAP and plasma Aβ1-42/Aβ1-40 ratio, a blood-based marker associated with brain Aβ load, in participants (65-90 years) categorised into low (Aβ-, n = 63) and high (Aβ+, n = 33) brain Aβ load groups via Aβ positron emission tomography.
- Plasma GFAP levels were significantly higher (p < 0.00001), and plasma Aβ1-42/Aβ1-40 ratios were significantly lower (p < 0.005), in Aβ+ participants compared to Aβ- participants, adjusted for covariates age, sex, and apolipoprotein E-ε4 carriage.
- These observations suggest that astrocytic damage or activation begins from the pre-symptomatic stage of AD and is associated with brain Aβ load.
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Study details
- Study designcross-sectional
- Participants63
- Effect sizeAUC = 0.78; AUC = 0.91; AUC = 0.92
- Evidence strengthLow
How this study scored 62/100
Published in a peer-reviewed 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 journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 36 of the 58 points we could judge it on, which is 62 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Translational psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 63 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33431793) |
| Free to read | 2 / 2 | Free to read |
| Points | 36 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 36 of the 58 points we could judge it on is 62 out of 100. |
| Total | 62 / 100 | — |
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APA 7th
Chatterjee, P., Pedrini, S., Stoops, E., Goozee, K., Villemagne, V. L., Asih, P. R., et al. (2021). Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer's disease. Translational psychiatry. https://doi.org/10.1038/s41398-020-01137-1
Vancouver
Chatterjee P, Pedrini S, Stoops E, Goozee K, Villemagne VL, Asih PR, et al. Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer's disease. Translational psychiatry. 2021. doi:10.1038/s41398-020-01137-1. PMID: 33431793.
BibTeX
@article{chatterjee2021-33431793,
author = {Chatterjee, P. and Pedrini, S. and Stoops, E. and Goozee, K. and Villemagne, V. L. and Asih, P. R. and Verberk, I. M. W. and Dave, P. and others},
title = {{Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer's disease}},
journal = {Translational psychiatry},
year = {2021},
doi = {10.1038/s41398-020-01137-1},
pmid = {33431793},
url = {https://doi.org/10.1038/s41398-020-01137-1}
}