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Blood Phosphorylated Tau 181 as a Biomarker for Amyloid Burden on Brain PET in Cognitively Healthy Adults
McGrath ER, Beiser AS, O'Donnell A, Yang Q, Ghosh S, Gonzales MM, Himali JJ, Satizabal CL et al.. Journal of Alzheimer's disease : JAD, 2022-01-01
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Background Plasma phosphorylated-tau181 (p-tau181) is a promising biomarker for Alzheimer's disease (AD) and may offer utility for predicting preclinical disease. Objective To evaluate the prospective association between plasma p-tau181 and amyloid-β (Aβ) and tau-PET deposition in cognitively unimpaired individuals. Methods Plasma p-tau181 levels were measured at baseline in 52 [48% women, mean 64.4 (SD 5.5) years] cognitively unimpaired Framingham Offspring cohort participants using samples stored between 2011-2014 who subsequently underwent 11C-Pittsburgh Compound-B (PiB)-PET and/or 18F-Flortaucipir (FTP)-PET scans (n = 18 with tau-PET) a mean of 6.8 (SD 0.6) years later. Our primary outcomes included Aβ-precuneus, Aβ-FLR (frontal, lateral, and retrosplenial cortices) and tau-global composite region PET deposition. Secondary outcomes included individual regional Aβ and tau PET-deposition. P-tau181 was compared with plasma neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) in predicting PET outcomes. Results P-tau181 was associated with increased Aβ deposition in the FLR (β±SE, 1.25±0.30, p < 0.0001), precuneus (1.35±0.29, p < 0.001), and other cortical regions. Plasma NFL (1.30±0.49, p = 0.01) and GFAP (1.46±0.39, p < 0.001) were also associated with FLR Aβ deposition. In models including all three biomarkers adjusted for age, sex, APOE E4 allele, AD polygenic risk score and cortical atrophy score, p-tau181 (0.93±0.31, p < 0.01, R2 = 0.18) and GFAP (0.93±0.41, p = 0.03, R2 = 0.11), but not NFL (0.25±0.51, p = 0.62, R2 = 0.01), were associated with FLR-Aβ deposition. Plasma p-tau181 was not associated with tau-PET burden. Conclusion In cognitively unimpaired adults, elevated plasma p-tau181 is associated with future increased Aβ deposition across multiple brain regions. Our results highlight the potential utility of p-tau181 as a blood-biomarker to screen for brain-amyloid deposition in cognitively healthy individuals in a community-setting.
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APA 7th
McGrath, E. R., Beiser, A. S., O'Donnell, A., Yang, Q., Ghosh, S., Gonzales, M. M., et al. (2022). Blood Phosphorylated Tau 181 as a Biomarker for Amyloid Burden on Brain PET in Cognitively Healthy Adults. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-215639
Vancouver
McGrath ER, Beiser AS, O'Donnell A, Yang Q, Ghosh S, Gonzales MM, et al. Blood Phosphorylated Tau 181 as a Biomarker for Amyloid Burden on Brain PET in Cognitively Healthy Adults. Journal of Alzheimer's disease : JAD. 2022. doi:10.3233/jad-215639. PMID: 35491781.
BibTeX
@article{mcgrath2022-35491781,
author = {McGrath, E. R. and Beiser, A. S. and O'Donnell, A. and Yang, Q. and Ghosh, S. and Gonzales, M. M. and Himali, J. J. and Satizabal, C. L. and others},
title = {{Blood Phosphorylated Tau 181 as a Biomarker for Amyloid Burden on Brain PET in Cognitively Healthy Adults}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2022},
doi = {10.3233/jad-215639},
pmid = {35491781},
url = {https://doi.org/10.3233/jad-215639}
}
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Key findings
- P-tau181 was compared with plasma neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) in predicting PET outcomes.
- Results P-tau181 was associated with increased Aβ deposition in the FLR (β±SE, 1.25±0.30, p < 0.0001), precuneus (1.35±0.29, p < 0.001), and other cortical regions.
- Plasma NFL (1.30±0.49, p = 0.01) and GFAP (1.46±0.39, p < 0.001) were also associated with FLR Aβ deposition.
- In models including all three biomarkers adjusted for age, sex, APOE E4 allele, AD polygenic risk score and cortical atrophy score, p-tau181 (0.93±0.31, p < 0.01, R2 = 0.18) and GFAP (0.93±0.41, p = 0.03, R2 = 0.11), but not NFL (0.25±0.51, p = 0.62, R2 = 0.01), were associated with FLR-Aβ deposition.
- Plasma p-tau181 was not associated with tau-PET burden.
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Study details
- Participants18
- Evidence strengthModerate
How this study scored 50/100
Published in a peer-reviewed journal. Scored zero for study design, 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 29 of the 58 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| 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 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 18 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 35491781) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 29 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 29 of the 58 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | — |
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