A Potential Diagnostic and Screening Aid in Alzheimer's Disease

Abdullah Hashmi, MD

March 23, 2022

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key Takeaways

  • The study determined that p-tau181/Aβ1-42 ratio was the highest performing test compared to individual measurements in predicting positive amyloid status from Aβ-PET.

  • Only the plasma p-tau181/Aβ1–42 ratio was strongly correlated with cerebrospinal fluid (CSF) p-tau181/Aβ1–42 ratio and was able to predict future cognitive decline within the cognitively normal subgroup.

Why This Matters

  • Alzheimer's disease (AD) is characterized by a preclinical and prodromal phase of >20 years. An understanding of the presence and severity of AD is improved when the markers amyloid beta (Aβ) and tau levels are considered simultaneously, according to clinicopathologic models.

  • Only one small study has investigated how plasma levels of Aβ and p-tau in combination are related to Aβ-PET burden. This study assessed whether p-tau181 and p-tau231 in a ratio with Aβ could improve predictions of Aβ burden over single analytes in comparison to PET or CSF sampling and whether the ratio could predict future cognitive decline and disease progression.

Study Design

  • This prospective, longitudinal cohort study enrolled adults older than 60. The patients underwent 18 monthly neuropsychological and clinical assessments and were classified either as clinically cognitively normal; as having mild cognitive impairment; or as having dementia. Only patients for whom CSF samples and Aβ-PET scans were available were included in the study.

  • Statistical analysis involved determining which plasma biomarkers and which ratios had the largest mean difference between Aβ-PET groups and whether they could predict Aβ-PET groups.

  • The study was also designed to analyze how well plasma biomarkers correlate to their corresponding CSF biomarkers and whether plasma biomarkers could predict CSF Aβ1–42 and cognitive decline.

Key Results

  • Of 333 participants for whom plasma was collected at first or second assessment, 43.5% of patients were positive on Aβ-PET.

  • Among all participants, the plasma p-tau181/AB1-42 ratio was able to best predict Aβ-PET (AUC = 0.905; 95% CI: .86 – .95).

  • From the cohort of 233 symptomatic patients with cognitive decline, the p-tau181/Aβ1–42 ratio was best at predicting Aβ-PET (AUC = 0.908; 95% CI: .82 – 1.00).

  • The plasma p-tau181/Aβ1–42 ratio correlated with CSF p-tau181 (Elecsys, Spearman's ρ = 0.74; P < .0001) and predicted abnormal CSF Aβ (AUC = 0.816; 95% CI: .74 – .89).

  • The p-tau181/Aβ1–42 ratio was able to predict future rates of cognitive decline, as assessed by Australian Imaging Biomarkers and Lifestyle Preclinical Alzheimer Cognitive Composite (AIBL-PACC) (P < .0001).

  • The plasma p-tau181/Aβ1–42 ratio predicted both Aβ-PET status and cognitive decline. It was the highest performing test compared to individual measurements in predicting amyloid positive status.


  • The study was unable to determine whether the p-tau181/Aβ ratio can act in place of CSF measurements.

  • Further investigations with extended longitudinal plasma collection points are necessary to determine disease chronicity.

  • Further longitudinal analyses with tau-PET measurement are necessary to determine p-tau231 effects.


  • The study was funded through the AIBL study and ADx Neurosciences in addition to public grants.

  • Eugeen Vanmechelen and Erik Stoops are shareholders of ADx Neurosciences. Jeroen Vanbrabant, Nele Dewit, and Kimberley Mauroo are employees of ADx Neurosciences. Paul Maruff is an employee of Cogstate Ltd.

  • Christopher Rowe has received research grants from NHMRC, Biogen, and AbbVie.

This is a summary of the preprint research study, "Plasma P-tau181/Aβ1–42 Ratio Predicts Aβ-PET Status and Correlates With CSF-P-tau181/Aβ1–42 and Future Cognitive Decline," written by researchers at the Florey Institute of Mental Health, Melbourne, VIC, Australia, and ADx Neurosciences, Ghent, Belgium, published on medRxiv and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.

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