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Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function
Lehmann S, Schraen-Maschke S, Vidal JS, Delaby C, Blanc F, Paquet C, Allinquant B, Bombois S et al.. Journal of neurology, neurosurgery, and psychiatry, 2023-04-03
Topic: Plasma and spinal-fluid biomarkers
Objectives Plasma P-tau181 is an increasingly established diagnostic marker for Alzheimer's disease (AD). Further validation in prospective cohorts is still needed, as well as the study of confounding factors that could influence its blood level. Methods This study is ancillary to the prospective multicentre Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk cohort that enrolled participants with mild cognitive impairment (MCI) who were examined for conversion to dementia for up to 3 years. Plasma Ptau-181 was measured using the ultrasensitive Quanterix HD-X assay. Results Among 476 MCI participants, 67% were amyloid positive (Aβ+) at baseline and 30% developed dementia. Plasma P-tau181 was higher in the Aβ+ population (3.9 (SD 1.4) vs 2.6 (SD 1.4) pg/mL) and in MCI that converted to dementia (3.8 (SD 1.5) vs 2.9 (SD 1.4) pg/mL). The addition of plasma P-tau181 to a logistic regression model combining age, sex, APOEε4 status and Mini Mental State Examination improved predictive performance (areas under the curve 0.691-0.744 for conversion and 0.786-0.849 for Aβ+). The Kaplan-Meier curve of conversion to dementia, according to the tertiles of plasma P-tau181, revealed a significant predictive value (Log rank p<0.0001) with an HR of 3.8 (95% CI 2.5 to 5.8). In addition, patients with plasma P-Tau(181) ≤2.32 pg/mL had a conversion rate of less than 20% over a 3-year period. Using a linear regression approach, chronic kidney disease, creatinine and estimated glomerular filtration rate were independently associated with plasma P-tau181 concentrations. Conclusions Plasma P-tau181 effectively detects Aβ+ status and conversion to dementia, confirming the value of this blood biomarker for the management of AD. However, renal function significantly modifies its levels and may thus induce diagnostic errors if not taken into account.
Key findings
- Results Among 476 MCI participants, 67% were amyloid positive (Aβ+) at baseline and 30% developed dementia.
- The Kaplan-Meier curve of conversion to dementia, according to the tertiles of plasma P-tau181, revealed a significant predictive value (Log rank p<0.0001) with an HR of 3.8 (95% CI 2.5 to 5.8).
- Using a linear regression approach, chronic kidney disease, creatinine and estimated glomerular filtration rate were independently associated with plasma P-tau181 concentrations.
- However, renal function significantly modifies its levels and may thus induce diagnostic errors if not taken into account.
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Study details
- Evidence strengthModerate
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people 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 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurology, neurosurgery, and psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| 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 37012068) |
| Free to read | 2 / 2 | Free to read |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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APA 7th
Lehmann, S., Schraen-Maschke, S., Vidal, J. S., Delaby, C., Blanc, F., Paquet, C., et al. (2023). Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function. Journal of neurology, neurosurgery, and psychiatry. https://doi.org/10.1136/jnnp-2022-330540
Vancouver
Lehmann S, Schraen-Maschke S, Vidal JS, Delaby C, Blanc F, Paquet C, et al. Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function. Journal of neurology, neurosurgery, and psychiatry. 2023. doi:10.1136/jnnp-2022-330540. PMID: 37012068.
BibTeX
@article{lehmann2023-37012068,
author = {Lehmann, S. and Schraen-Maschke, S. and Vidal, J. S. and Delaby, C. and Blanc, F. and Paquet, C. and Allinquant, B. and Bombois, S. and others},
title = {{Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function}},
journal = {Journal of neurology, neurosurgery, and psychiatry},
year = {2023},
doi = {10.1136/jnnp-2022-330540},
pmid = {37012068},
url = {https://doi.org/10.1136/jnnp-2022-330540}
}