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Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer's disease
Devanarayan V, Doherty T, Charil A, Sachdev P, Ye Y, Murali LK, Llano DA, Zhou J et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024-06-28
Topic: Amyloid, tau and blood-test diagnosis
Background This study investigated the potential of phosphorylated plasma Tau217 ratio (pTau217R) and plasma amyloid beta (Aβ) 42/Aβ40 in predicting brain amyloid levels measured by positron emission tomography (PET) Centiloid (CL) for Alzheimer's disease (AD) staging and screening. Methods Quantification of plasma pTau217R and Aβ42/Aβ40 employed immunoprecipitation-mass spectrometry. CL prediction models were developed on a cohort of 904 cognitively unimpaired, preclinical and early AD subjects and validated on two independent cohorts. Results Models integrating pTau217R outperformed Aβ42/Aβ40 alone, predicting amyloid levels up to 89.1 CL. High area under the receiver operating characteristic curve (AUROC) values (89.3% to 94.7%) were observed across a broad CL range (15 to 90). Utilizing pTau217R-based models for low amyloid levels reduced PET scans by 70.5% to 78.6%. Discussion pTau217R effectively predicts brain amyloid levels, surpassing cerebrospinal fluid Aβ42/Aβ40's range. Combining it with plasma Aβ42/Aβ40 enhances sensitivity for low amyloid detection, reducing unnecessary PET scans and expanding clinical utility. Clinicaltrials Gov identifiers NCT02956486 (MissionAD1), NCT03036280 (MissionAD2), NCT04468659 (AHEAD3-45), NCT03887455 (ClarityAD) HIGHLIGHTS: Phosphorylated plasma Tau217 ratio (pTau217R) effectively predicts amyloid-PET Centiloid (CL) across a broad spectrum. Integrating pTau217R with Aβ42/Aβ40 extends the CL prediction upper limit to 89.1 CL. Combined model predicts amyloid status with high accuracy, especially in cognitively unimpaired individuals. This model identifies subjects above or below various CL thresholds with high accuracy. pTau217R-based models significantly reduce PET scans by up to 78.6% for screening out individuals with no/low amyloid.
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APA 7th
Devanarayan, V., Doherty, T., Charil, A., Sachdev, P., Ye, Y., Murali, L. K., et al. (2024). Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.14073
Vancouver
Devanarayan V, Doherty T, Charil A, Sachdev P, Ye Y, Murali LK, et al. Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. doi:10.1002/alz.14073. PMID: 38940656.
BibTeX
@article{devanarayan2024-38940656,
author = {Devanarayan, V. and Doherty, T. and Charil, A. and Sachdev, P. and Ye, Y. and Murali, L. K. and Llano, D. A. and Zhou, J. and others},
title = {{Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer's disease}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2024},
doi = {10.1002/alz.14073},
pmid = {38940656},
url = {https://doi.org/10.1002/alz.14073}
}
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Key findings
- Results Models integrating pTau217R outperformed Aβ42/Aβ40 alone, predicting amyloid levels up to 89.1 CL.
- This model identifies subjects above or below various CL thresholds with high accuracy. pTau217R-based models significantly reduce PET scans by up to 78.6% for screening out individuals with no/low amyloid.
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Study details
- Effect size89.3% to 94.7%; 70.5% to 78.6%; 78.6%
- Evidence strengthModerate
How this study scored 55/100
Published in a leading specialty journal. Scored zero for study design, sample size, 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 32 of the 58 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| 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 | 4 / 5 | 2024 — within 3 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 38940656) |
| Free to read | 2 / 2 | Free to read |
| Points | 32 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 32 of the 58 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
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