Alzheimer's disease (AD) is a devastating condition, and with recent developments in anti-AD therapies, there's a growing need for cost-effective methods
to identify AD-related changes in patients with cognitive impairment. A new study explores the potential of blood biomarkers to revolutionize AD diagnosis,
reducing the need for more invasive and costly procedures.
Researchers conducted a study involving 348 patients with mild cognitive impairment (MCI) in two separate memory clinic-based cohorts.
They aimed to develop a two-step diagnostic workflow for detecting amyloid-β (Aβ) positivity, a hallmark of AD, by incorporating blood-based
biomarkers.
The Two-Step Workflow:
Step 1: A Blood-Based Model In the first step, the researchers developed a blood-based model that considered three key factors:
plasma tau protein 217 (p-tau217) levels, age, and the presence of the APOE ε4 gene variant. This model accurately stratified patients
into low, intermediate, or high-risk groups for Aβ positivity. It demonstrated excellent accuracy, with an area under the curve (AUC)
of 89.3% in the initial cohort and 94.3% in the validation cohort.
Step 2: Confirmatory Testing In the second step, patients in the intermediate-risk group were referred for cerebrospinal fluid (CSF)
Aβ42/Aβ40 testing, while those in the low- and high-risk groups had their Aβ status determined solely based on the blood-based model
from step 1.
Depending on the chosen risk threshold in step 1 (lenient, moderate, or stringent), the two-step workflow achieved an overall accuracy
of 88.2%, 90.5%, or 92.0% in detecting Aβ-PET status. Importantly, it significantly reduced the number of necessary CSF tests by 85.9%,
72.7%, or 61.2%, respectively.
Secondary analyses further confirmed the effectiveness of this approach in a different cohort using an adapted version of the blood-based
model. This demonstrates its robustness across various patient populations.
In conclusion, this groundbreaking study presents a promising avenue for cost-effective AD diagnosis in memory clinic settings.
By utilizing a simple blood test that factors in p-tau217 levels, age, and APOE ε4 status, clinicians can accurately stratify patients,
reducing the need for more invasive and expensive procedures like CSF or positron emission tomography (PET) tests. This two-step workflow
not only enhances diagnostic accuracy but also offers a more accessible and affordable means of detecting AD pathology. It represents
a significant step forward in the fight against Alzheimer's disease and offers hope for earlier detection and intervention.
Citations:
Brum, W.S., Cullen, N.C., Janelidze, S. et al. A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases. Nat Aging 3,
1079–1090 (2023).
https://www.nature.com/articles/s43587-023-00471-5