A potential aid in the diagnosis and screening of Alzheimer’s disease

The study covered in this summary has been published on medRxiv.org as a preprint and has not yet been peer-reviewed.

Key points to remember

  • The study determined that p-tau181/Aβ1-42 ratio was the best 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 the cerebrospinal fluid (CSF) p-tau181/Aβ1–42 ratio and was able to predict future cognitive decline in the cognitively normal subgroup.

why it 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 enhanced when amyloid beta (Aβ) and tau markers are considered simultaneously, according to clinicopathologic models.

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

study design

  • This prospective longitudinal cohort study recruited adults over the age of 60. Patients underwent 18 monthly neuropsychological and clinical assessments and were classified as either clinically cognitive normal; as having mild cognitive impairment; or as suffering from dementia. Only patients for whom CSF samples and Aβ-PET scans were available were included in the study.

  • Statistical analysis was to determine which plasma biomarkers and ratios had the greatest 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 with their corresponding biomarkers in CSF and whether plasma biomarkers could predict CSF Aβ1–42 and cognitive decline.

Principle results

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

  • Among all participants, the plasma p-tau181/AB1-42 ratio was able to best predict Aβ-PET (AUC = 0.905; 95% CI: 0.86, 0.95).

  • In the cohort of 233 symptomatic patients with cognitive decline, the p-tau181/Aβ1–42 ratio was the best predictor of Aβ-PET (AUC = 0.908; 95% CI: 0.82, 1.00).

  • The plasma p-tau181/Aβ1–42 ratio was correlated with CSF p-tau181 (Elecsys, Spearman’s ρ = 0.74; P

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

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

Limits

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

  • Further investigations with extended longitudinal plasma collection points are needed to determine the chronicity of the disease.

  • Further longitudinal analyzes with tau-PET measurement are needed to determine the effects of p-tau231.

Disclosures

  • The study was funded by the AIBL Study and ADx Neurosciences in addition to government grants.

  • Eugene 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 an abstract of the pre-print 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 from the Florey Institute of Mental Health, Melbourne, VIC, Australia, and ADx Neurosciences, Ghent, Belgium, published on medRxiv and made available to you by Medscape. This study has not yet been peer reviewed. The full text of the study is available at medRxiv.org.

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