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Elevated Plasma Phosphorylated Tau 181 in Amyotrophic Lateral Sclerosis
Cousins KAQ, Shaw LM, Shellikeri S, Dratch L, Rosario L, Elman LB, Quinn C, Amado DA et al.. Annals of neurology, 2022-08-17
Topic: Brain proteins, microglia and lab models
Objective Plasma phosphorylated tau (p-tau 181 ) is reliably elevated in Alzheimer's disease (AD), but less explored is its specificity relative to other neurodegenerative conditions. Here, we find novel evidence that plasma p-tau 181 is elevated in amyotrophic lateral sclerosis (ALS), a neurodegenerative condition typically lacking tau pathology. We performed a detailed evaluation to identify the clinical correlates of elevated p-tau 181 in ALS. Methods Patients were clinically or pathologically diagnosed with ALS (n = 130) or AD (n = 79), or were healthy non-impaired controls (n = 26). Receiver operating characteristic (ROC) curves were analyzed and area under the curve (AUC) was used to discriminate AD from ALS. Within ALS, Mann-Whitney-Wilcoxon tests compared analytes by presence/absence of upper motor neuron and lower motor neuron (LMN) signs. Spearman correlations tested associations between plasma p-tau 181 and postmortem neuron loss. Results A Wilcoxon test showed plasma p-tau 181 was higher in ALS than controls (W = 2,600, p = 0.000015), and ROC analyses showed plasma p-tau 181 poorly discriminated AD and ALS (AUC = 0.60). In ALS, elevated plasma p-tau 181 was associated with LMN signs in cervical (W = 827, p = 0.0072), thoracic (W = 469, p = 0.00025), and lumbosacral regions (W = 851, p = 0.0000029). In support of LMN findings, plasma p-tau 181 was associated with neuron loss in the spinal cord (rho = 0.46, p = 0.017), but not in the motor cortex (p = 0.41). Cerebrospinal spinal fluid p-tau 181 and plasma neurofilament light chain were included as reference analytes, and demonstrate specificity of findings. Interpretation We found strong evidence that plasma p-tau 181 is elevated in ALS and may be a novel marker specific to LMN dysfunction. ANN NEUROL 2022;92:807-818.
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APA 7th
Cousins, K. A. Q., Shaw, L. M., Shellikeri, S., Dratch, L., Rosario, L., Elman, L. B., et al. (2022). Elevated Plasma Phosphorylated Tau 181 in Amyotrophic Lateral Sclerosis. Annals of neurology. https://doi.org/10.1002/ana.26462
Vancouver
Cousins KAQ, Shaw LM, Shellikeri S, Dratch L, Rosario L, Elman LB, et al. Elevated Plasma Phosphorylated Tau 181 in Amyotrophic Lateral Sclerosis. Annals of neurology. 2022. doi:10.1002/ana.26462. PMID: 35877814.
BibTeX
@article{cousins2022-35877814,
author = {Cousins, K. A. Q. and Shaw, L. M. and Shellikeri, S. and Dratch, L. and Rosario, L. and Elman, L. B. and Quinn, C. and Amado, D. A. and others},
title = {{Elevated Plasma Phosphorylated Tau 181 in Amyotrophic Lateral Sclerosis}},
journal = {Annals of neurology},
year = {2022},
doi = {10.1002/ana.26462},
pmid = {35877814},
url = {https://doi.org/10.1002/ana.26462}
}
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Key findings
- Results A Wilcoxon test showed plasma p-tau 181 was higher in ALS than controls (W = 2,600, p = 0.000015), and ROC analyses showed plasma p-tau 181 poorly discriminated AD and ALS (AUC = 0.60).
- In ALS, elevated plasma p-tau 181 was associated with LMN signs in cervical (W = 827, p = 0.0072), thoracic (W = 469, p = 0.00025), and lumbosacral regions (W = 851, p = 0.0000029).
- In support of LMN findings, plasma p-tau 181 was associated with neuron loss in the spinal cord (rho = 0.46, p = 0.017), but not in the motor cortex (p = 0.41).
- Interpretation We found strong evidence that plasma p-tau 181 is elevated in ALS and may be a novel marker specific to LMN dysfunction.
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Study details
- Participants130
- Effect sizeAUC = 0.60
- Evidence strengthLow
How this study scored 57/100
Published in a leading specialty journal. Scored zero for study design 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 33 of the 58 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of neurology) |
| 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 | 1 / 5 | Rated “low” 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 | 2 / 4 | 130 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 35877814) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 33 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 33 of the 58 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
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