Home › Research › Tau biomarkers
Novel CSF tau biomarkers can be used for disease staging of sporadic Alzheimer's disease
Gemma Salvadó, Kanta Horie, Nicolas R Barthélemy, Jacob W Vogel, Alexa Pichet Binette, Charles D Chen, Andrew J Aschenbrenner, Brian A Gordon et al.. medRxiv : the preprint server for health sciences, 2023-07-16
Topic: Plasma and spinal-fluid biomarkers
Biological staging of individuals with Alzheimer's disease (AD) may improve diagnostic and prognostic work-up of dementia in clinical practice and the design of clinical trials. Here, we created a staging model using the Subtype and Stage Inference (SuStaIn) algorithm by evaluating cerebrospinal fluid (CSF) amyloid-β (Aβ) and tau biomarkers in 426 participants from BioFINDER-2, that represent the entire spectrum of AD. The model composition and main analyses were replicated in 222 participants from the Knight ADRC cohort. SuStaIn revealed in the two cohorts that the data was best explained by a single biomarker sequence (one subtype), and that five CSF biomarkers (ordered: Aβ42/40, tau phosphorylation occupancies at the residues 217 and 205 [pT217/T217 and pT205/T205], microtubule-binding region of tau containing the residue 243 [MTBR-tau243], and total tau) were sufficient to create an accurate disease staging model. Increasing CSF stages (0-5) were associated with increased abnormality in other AD-related biomarkers, such as Aβ- and tau-PET, and aligned with different phases of longitudinal biomarker changes consistent with current models of AD progression. Higher CSF stages at baseline were associated with higher hazard ratio of clinical decline. Our findings indicate that a common pathophysiologic molecular pathway develops across all AD patients, and that a single CSF collection is sufficient to reliably indicate the presence of both AD pathologies and the degree and stage of disease progression.
Key findings
- SuStaIn revealed in the two cohorts that the data was best explained by a single biomarker sequence (one subtype), and that five CSF biomarkers (ordered: Aβ42/40, tau phosphorylation occupancies at the residues 217 and 205 [pT217/T217 and pT205/T205], microtubule-binding region of tau containing the residue 243 [MTBR-tau243], and total tau) were sufficient to create an accurate disease staging model.
- Increasing CSF stages (0-5) were associated with increased abnormality in other AD-related biomarkers, such as Aβ- and tau-PET, and aligned with different phases of longitudinal biomarker changes consistent with current models of AD progression.
- Higher CSF stages at baseline were associated with higher hazard ratio of clinical decline.
- Our findings indicate that a common pathophysiologic molecular pathway develops across all AD patients, and that a single CSF collection is sufficient to reliably indicate the presence of both AD pathologies and the degree and stage of disease progression.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designlongitudinal study
- Participants426
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 43 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on 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, multi-centre collaboration and free to read, so those were left out: it earned 26 of the 60 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv : the preprint server for health sciences) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 426 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 37503281) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 26 / 60 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 60 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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
Salvadó, G., Horie, K., Barthélemy, N. R., Vogel, J. W., Binette, A. P., Chen, C. D., et al. (2023). Novel CSF tau biomarkers can be used for disease staging of sporadic Alzheimer's disease. medRxiv : the preprint server for health sciences. https://doi.org/10.1101/2023.07.14.23292650
Vancouver
Salvadó G, Horie K, Barthélemy NR, Vogel JW, Binette AP, Chen CD, et al. Novel CSF tau biomarkers can be used for disease staging of sporadic Alzheimer's disease. medRxiv : the preprint server for health sciences. 2023. doi:10.1101/2023.07.14.23292650. PMID: 37503281.
BibTeX
@article{salvado2023-37503281,
author = {Salvadó, Gemma and Horie, Kanta and Barthélemy, Nicolas R and Vogel, Jacob W and Binette, Alexa Pichet and Chen, Charles D and Aschenbrenner, Andrew J and Gordon, Brian A and others},
title = {{Novel CSF tau biomarkers can be used for disease staging of sporadic Alzheimer's disease}},
journal = {medRxiv : the preprint server for health sciences},
year = {2023},
doi = {10.1101/2023.07.14.23292650},
pmid = {37503281},
url = {https://doi.org/10.1101/2023.07.14.23292650}
}