Plasma p‐tau181 concentration accurately predicts clinically diagnosed Alzheimer’s Disease cases
Bibliographic record
Abstract
Abstract Background The feasibility of detecting tau phosphorylated at threonine‐181(p‐tau181) in CSF makes it a valuable biomarker for diagnosis in the field of Alzheimer’s Disease (AD). Recently, the novel technologies accurately measuring biomarkers directly in blood offer a unique advantage for use in clinical testing and trials. This study describes the performance testing of a novel plasma p‐tau181 Simoa assay to predict clinical AD. Method The presented data were obtained after analysis of EDTA plasma from cases with clinical AD who had been referred to the UBC Hospital Clinic with complaint of cognitive impairment and were assessed for dementia and AD between 2008 – 2018. We also analysed serum of 50 random healthy donors and 50 aged ‐ matched controls with normal cognition. The samples were assayed using an ADx Neurosciences developed p‐tau181 specific Simoa assay. Analytical performance (precision, detection limit, parallelism) and analyte stability was evaluated using healthy‐donor samples. Finally, the p‐tau181 specificity was assessed using synthetic peptides. Result 254 AD patients (female = 125) and 100 controls (female = 39) were included. The average of plasma p‐tau181 was 72.9 ±36.8 ng/L in AD cases and the average of serum p‐tau181 was 8.1± 10.5 ng/L in controls. The concentration of plasma p‐tau181 in patients with AD was significantly increased with at‐least 9‐fold versus controls (p=<0.001). ROC analysis demonstrated an AUC of 0.92 and a suitable clinical cut‐off of 34.3 ng/L. Analytical performance testing: 1 of the 254 AD samples tested were below the LLOQ of 1.38 ng/L. The intra‐ and inter‐ assay variability was 8.2% CV and 11.8 % CV, respectively. Sample dilution (df 2‐4‐5‐6) resulted in mean parallelism of 93.5 %. P‐tau181 levels were stable up to 5 Freeze/Thaw cycle (mean 98.9%) and up to 24h at 4°C or RT. The assay was found to be highly specific towards p‐tau181 and nonreactive to p‐tau175. Conclusion The plasma p‐tau181 concentration in AD cases were significantly higher than controls with limited overlap and in line with published data. The specific measurement of plasma p‐tau181 shows good promise in offering a non‐biased measurement and help in the clinical assessment of AD patients and clinical trials.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".