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Plasma phosphorylated tau 217 in preclinical Alzheimer's disease
Jonaitis EM, Janelidze S, Cody KA, Langhough R, Du L, Chin NA, Mattsson-Carlgren N, Hogan KJ et al.. Brain communications, 2023-03-06
Topic: Plasma and spinal-fluid biomarkers
Plain-language summary
An accurate blood test for Alzheimer's disease that is sensitive to preclinical proteinopathy and cognitive decline has clear implications for early detection and secondary prevention. We assessed the performance of plasma phosphorylated tau 217 ( pTa u 217 ) against brain PET markers of amyloid [ [ 11 C ] -labelled Pittsburgh compound B (PiB)] and tau ( [ 18 F ] MK-6240) and its utility for predicting longitudinal cognition. Samples were analysed from a subset of participants with up to 8 years follow-up in the Wisconsin Registry for Alzheimer's Prevention (WRAP; 2001-present; plasma 2011-present), a longitudinal cohort study of adults from midlife, enriched for parental history of Alzheimer's disease. Participants were a convenience sample who volunteered for at least one PiB scan, had usable banked plasma and were cognitively unimpaired at first plasma collection. Study personnel who interacted with participants or samples were blind to amyloid status. We used mixed effects models and receiver-operator characteristic curves to assess concordance between plasma pTa u 217 and PET biomarkers of Alzheimer's disease and mixed effects models to understand the ability of plasma pTa u 217 to predict longitudinal performance on WRAP's preclinical Alzheimer's cognitive composite (PACC-3). The primary analysis included 165 people (108 women; mean age = 62.9 ± 6.06; 160 still enrolled; 2 deceased; 3 discontinued). Plasma pTa u 217 was strongly related to PET-based estimates of concurrent brain amyloid ( β ^ = 0.83 (0.75, 0.90), P < 0.001). Concordance was high between plasma pTa u 217 and both amyloid PET (area under the curve = 0.91, specificity = 0.80, sensitivity = 0.85, positive predictive value = 0.58, negative predictive value = 0.94) and tau PET (area under the curve = 0.95, specificity = 1, sensitivity = 0.85, positive predictive value = 1, negative predictive value = 0.98). Higher baseline pTa u 217 levels were associated with worse cognitive trajectories ( β ^ p T a u × a g e = -0.07 (-0.09, -0.06), P < 0.001). In a convenience sample of unimpaired adults, plasma pTa u 217 levels correlate well with concurrent brain Alzheimer's disease pathophysiology and with prospective cognitive performance. These data indicate that this marker can detect disease before clinical signs and thus may disambiguate presymptomatic Alzheimer's disease from normal cognitive ageing.
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APA 7th
Jonaitis, E. M., Janelidze, S., Cody, K. A., Langhough, R., Du, L., Chin, N. A., et al. (2023). Plasma phosphorylated tau 217 in preclinical Alzheimer's disease. Brain communications. https://doi.org/10.1093/braincomms/fcad057
Vancouver
Jonaitis EM, Janelidze S, Cody KA, Langhough R, Du L, Chin NA, et al. Plasma phosphorylated tau 217 in preclinical Alzheimer's disease. Brain communications. 2023. doi:10.1093/braincomms/fcad057. PMID: 37013174.
BibTeX
@article{jonaitis2023-37013174,
author = {Jonaitis, E. M. and Janelidze, S. and Cody, K. A. and Langhough, R. and Du, L. and Chin, N. A. and Mattsson-Carlgren, N. and Hogan, K. J. and others},
title = {{Plasma phosphorylated tau 217 in preclinical Alzheimer's disease}},
journal = {Brain communications},
year = {2023},
doi = {10.1093/braincomms/fcad057},
pmid = {37013174},
url = {https://doi.org/10.1093/braincomms/fcad057}
}
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Key findings
- Higher baseline pTa u 217 levels were associated with worse cognitive trajectories ( β ^ p T a u × a g e = -0.07 (-0.09, -0.06), P < 0.001).
- These data indicate that this marker can detect disease before clinical signs and thus may disambiguate presymptomatic Alzheimer's disease from normal cognitive ageing.
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Study details
- Study designcohort study
- Participants165
- Evidence strengthModerate
How this study scored 71/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for effect reported and randomized / 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 multicenter collaboration, so those were left out: it earned 41 of the 58 points we could judge it on, which is 71 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain communications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A cohort study following 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 | 165 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) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37013174) |
| Free to read | 2 / 2 | Free to read |
| Points | 41 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 41 of the 58 points we could judge it on is 71 out of 100. |
| Total | 71 / 100 | — |
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