Filenews 4 September 2023
A new biomarker tested with a simple blood test comes to diagnose Alzheimer's disease with great accuracy. The biomarker p-tau217 can with high accuracy detect or rule out brain amyloidosis, the most significant and early damage caused by the disease.
Researchers from the Universities of Gothenburg in Sweden and Lund and Montreal in Canada published their study in Nature Aging.
In recent years, a lot of effort has been made to develop biomarkers that through blood tests could diagnose Alzheimer's disease. Scientists have focused on the tau protein, particularly its phosphorylated variant (p-tau), as one of the main proteins involved in the pathology of Alzheimer's disease.
New blood-based p-tau biomarkers, specifically a variant called p-tau217, have shown promise as clinically useful tools for screening patients with memory problems or other early cognitive symptoms suggestive of early Alzheimer's disease.
However, concerns remain about the accuracy of the results, in terms of false positive or negative results, especially when the disease is confirmed by other tests such as imaging of amyloid plaques with PET/CT (positron emission computed tomography).
Considering not only the ethical and psychological concerns caused by possible misdiagnosis, but also the high costs and potential medical risks of starting treatments in people who do not have the disease), scientists at the University of Gothenburg and their colleagues developed a new strategy for the clinical application of blood biomarkers.
Two steps to diagnosis
The researchers adopted a two-step model.
The first step involves a diagnostic model based on plasma p-tau217, combined with age and APOE e4, to identify patients with mild cognitive impairment (MCI) for risk of amyloid PET/CT positivity.
The second step includes confirmatory tests based on ratio 2 based on confirmatory tests with the ratio of amyloid beta 42 and 40 in cerebrospinal fluid or amyloid PET/CT. This procedure will apply to people with uncertain outcomes from the first step.
The two-step model was evaluated in 348 patients with mild cognitive impairment by the Swedish BioFINDER studies (University of Lund) and validated in the independent TRIAD group (McGill University, Montreal, Canada) also using an independent method for the analysis of p-tau217 plasma.
High precision
The model was evaluated on three different threshold strategies for categorizing patients with Alzheimer's disease-like pathology into groups according to the degree of risk (low, medium and high) of testing positive for amyloid beta.
At the strict thresholds of sensitivity and specificity with 97.5% sensitivity (to avoid not detecting patients who are positive in the amyloid beta test), only 6.6% were found false negatives, while the strict specificity of 97.5% (to avoid classifying patients who are negative in the high risk beta amyloid test) gave only 2.3% false positives.
Within the strict sensitivity/specificity limits, 41% of patients belonged to the intermediate risk group (versus 29% of patients for the 95% range).
Further evaluations of this group with beta amyloid 42 and 40 ratio tests in cerebrospinal fluid showed 86% agreement with amyloid PET imaging results. The results were verified by McGill's independent patient panel.
Screening
The two-step model based on p-tau217 plasma to determine the risk of patients with mild cognitive impairment at high, low and intermediate risk of amyloidosis and early pathology of Alzheimer's disease has shown that it may contribute significantly to the need for confirmatory screening with cerebrospinal fluid examination or PET/CT imaging.
In particular, in high-risk patients, if a diagnosis arises to start symptomatic treatment or if there is no diagnosis yet, they may be referred in the future for the initiation of specialized disease-modifying therapy.
In the low-risk group, Alzheimer's disease can be ruled out with a high degree of certainty.
The intermediate risk group comprises only about one third of patients, which is expected to substantially reduce the need for confirmatory cerebrospinal fluid or PET testing in the specialised clinic, and therefore cost savings for society.
Specifically, according to the study, the use of the new biomarker, depending on whether mild, moderate or strict limits were used in step 1, the workflow accuracy for detecting PET β-amyloid status was 88.2%, 90.5% and 92.0%, respectively, while reducing the number of necessary cerebrospinal fluid tests by 85.9%, 72.7% and 61.2%, respectively.
philenews / in.gr
