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Site-Specific Cerebrospinal Fluid Tau Hyperphosphorylation in Response to Alzheimer's Disease Brain Pathology: Not All Tau Phospho-Sites are Hyperphosphorylated
Barthélemy NR, Toth B, Manser PT, Sanabria-Bohórquez S, Teng E, Keeley M, Bateman RJ, Weimer RM et al.. Journal of Alzheimer's disease : JAD, 2022-01-01
Topic: Brain proteins, microglia and lab models
Background Understanding patterns of association between CSF phosphorylated tau (p-tau) species and clinical disease severity will aid Alzheimer's disease (AD) diagnosis and treatment. Objective To evaluate changes in tau phosphorylation ratios to brain imaging (amyloid PET, [18F]GTP1 PET, and MRI) and cognition across clinical stages of AD in two different cohorts. Methods A mass spectrometry (MS)-based method was used to evaluate the relationship between p-tau/tau phosphorylation ratios on 11 sites in CSF and AD pathology measured by tau PET ([18F]GTP1) and amyloid PET ([18F]florbetapir or [18F]florbetaben). Cohort A included cognitively normal amyloid negative (n = 6) and positive (n = 5) individuals, and amyloid positive prodromal (n = 13), mild (n = 12), and moderate AD patients (n = 10); and Cohort B included amyloid positive prodromal (n = 24) and mild (n = 40) AD patients. Results In this cross-sectional analysis, we identified clusters of phosphosites with different profiles of phosphorylation ratios across stages of disease. Eight of 11 investigated sites were hyperphosphorylated and associated with SUVR measures from [18F]GTP1 and amyloid PET. Novel sites 111, 153, and 208 may be relevant biomarkers for AD diagnosis to complement tau hyperphosphorylation measures on previously established sites 181, 205, 217, and 231. Hypophosphorylation was detected on residues 175, 199, and 202, and was inversely associated with [18F]GTP1 and amyloid PET. Conclusion Hyperphosphorylated and hypophosphorylated forms of tau are associated with AD pathologies, and due to their different site-specific profiles, they may be used in combination to assist with staging of disease.
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APA 7th
Barthélemy, N. R., Toth, B., Manser, P. T., Sanabria-Bohórquez, S., Teng, E., Keeley, M., et al. (2022). Site-Specific Cerebrospinal Fluid Tau Hyperphosphorylation in Response to Alzheimer's Disease Brain Pathology: Not All Tau Phospho-Sites are Hyperphosphorylated. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-210677
Vancouver
Barthélemy NR, Toth B, Manser PT, Sanabria-Bohórquez S, Teng E, Keeley M, et al. Site-Specific Cerebrospinal Fluid Tau Hyperphosphorylation in Response to Alzheimer's Disease Brain Pathology: Not All Tau Phospho-Sites are Hyperphosphorylated. Journal of Alzheimer's disease : JAD. 2022. doi:10.3233/jad-210677. PMID: 34806603.
BibTeX
@article{barthelemy2022-34806603,
author = {Barthélemy, N. R. and Toth, B. and Manser, P. T. and Sanabria-Bohórquez, S. and Teng, E. and Keeley, M. and Bateman, R. J. and Weimer, R. M. and others},
title = {{Site-Specific Cerebrospinal Fluid Tau Hyperphosphorylation in Response to Alzheimer's Disease Brain Pathology: Not All Tau Phospho-Sites are Hyperphosphorylated}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2022},
doi = {10.3233/jad-210677},
pmid = {34806603},
url = {https://doi.org/10.3233/jad-210677}
}
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Key findings
- Results In this cross-sectional analysis, we identified clusters of phosphosites with different profiles of phosphorylation ratios across stages of disease.
- Eight of 11 investigated sites were hyperphosphorylated and associated with SUVR measures from [18F]GTP1 and amyloid PET.
- Hypophosphorylation was detected on residues 175, 199, and 202, and was inversely associated with [18F]GTP1 and amyloid PET.
- Conclusion Hyperphosphorylated and hypophosphorylated forms of tau are associated with AD pathologies, and due to their different site-specific profiles, they may be used in combination to assist with staging of disease.
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Study details
- Study designcross-sectional
- Evidence strengthModerate
How this study scored 53/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for 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 31 of the 58 points we could judge it on, which is 53 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 | 4 / 12 | A snapshot of people at one point in 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 | 2022 — 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 34806603) |
| Free to read | 2 / 2 | Free to read |
| Points | 31 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 31 of the 58 points we could judge it on is 53 out of 100. |
| Total | 53 / 100 | — |
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