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Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads
Salvadó G, Ossenkoppele R, Ashton NJ, Beach TG, Serrano GE, Reiman EM, Zetterberg H, Mattsson-Carlgren N et al.. EMBO molecular medicine, 2023-03-13
Topic: Plasma and spinal-fluid biomarkers
Several promising plasma biomarkers for Alzheimer's disease have been recently developed, but their neuropathological correlates have not yet been fully determined. To investigate and compare independent associations between multiple plasma biomarkers (p-tau181, p-tau217, p-tau231, Aβ42/40, GFAP, and NfL) and neuropathologic measures of amyloid and tau, we included 105 participants from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) with antemortem plasma samples and a postmortem neuropathological exam, 48 of whom had longitudinal p-tau217 and p-tau181. When simultaneously including plaque and tangle loads, the Aβ42/40 ratio and p-tau231 were only associated with plaques (ρ Aβ42/40 [95%CI] = -0.53[-0.65, -0.35], ρ p-tau231 [95%CI] = 0.28[0.10, 0.43]), GFAP was only associated with tangles (ρ GFAP [95%CI] = 0.39[0.17, 0.57]), and p-tau217 and p-tau181 were associated with both plaques (ρ p-tau217 [95%CI] = 0.40[0.21, 0.56], ρ p-tau181 [95%CI] = 0.36[0.15, 0.50]) and tangles (ρ p-tau217 [95%CI] = 0.52[0.34, 0.66]; ρ p-tau181 [95%CI] = 0.36[0.17, 0.52]). A model combining p-tau217 and the Aβ42/40 ratio showed the highest accuracy for predicting the presence of Alzheimer's disease neuropathological change (ADNC, AUC[95%CI] = 0.89[0.82, 0.96]) and plaque load (R 2 = 0.55), while p-tau217 alone was optimal for predicting tangle load (R 2 = 0.45). Our results suggest that high-performing assays of plasma p-tau217 and Aβ42/40 might be an optimal combination to assess Alzheimer's-related pathology in vivo.
Key findings
- When simultaneously including plaque and tangle loads, the Aβ42/40 ratio and p-tau231 were only associated with plaques (ρ Aβ42/40 [95%CI] = -0.53[-0.65, -0.35], ρ p-tau231 [95%CI] = 0.28[0.10, 0.43]), GFAP was only associated with tangles (ρ GFAP [95%CI] = 0.39[0.17, 0.57]), and p-tau217 and p-tau181 were associated with both plaques (ρ p-tau217 [95%CI] = 0.40[0.21, 0.56], ρ p-tau181 [95%CI] = 0.36[0.15, 0.50]) and tangles (ρ p-tau217 [95%CI] = 0.52[0.34, 0.66]; ρ p-tau181 [95%CI] = 0.36[0.17, 0.52]).
- Our results suggest that high-performing assays of plasma p-tau217 and Aβ42/40 might be an optimal combination to assess Alzheimer's-related pathology in vivo.
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Study details
- Study designlongitudinal study
- Participants105
- Evidence strengthModerate
How this study scored 67/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and 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 39 of the 58 points we could judge it on, which is 67 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (EMBO molecular medicine) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A longitudinal study following the same 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 | 2 / 4 | 105 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 | — / 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 36912178) |
| Free to read | 2 / 2 | Free to read |
| Points | 39 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 39 of the 58 points we could judge it on is 67 out of 100. |
| Total | 67 / 100 | — |
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APA 7th
Salvadó, G., Ossenkoppele, R., Ashton, N. J., Beach, T. G., Serrano, G. E., Reiman, E. M., et al. (2023). Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads. EMBO molecular medicine. https://doi.org/10.15252/emmm.202217123
Vancouver
Salvadó G, Ossenkoppele R, Ashton NJ, Beach TG, Serrano GE, Reiman EM, et al. Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads. EMBO molecular medicine. 2023. doi:10.15252/emmm.202217123. PMID: 36912178.
BibTeX
@article{salvado2023-36912178,
author = {Salvadó, G. and Ossenkoppele, R. and Ashton, N. J. and Beach, T. G. and Serrano, G. E. and Reiman, E. M. and Zetterberg, H. and Mattsson-Carlgren, N. and others},
title = {{Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads}},
journal = {EMBO molecular medicine},
year = {2023},
doi = {10.15252/emmm.202217123},
pmid = {36912178},
url = {https://doi.org/10.15252/emmm.202217123}
}