A new research study, published this week in the Journal of the American Medical Association (JAMA) and presented at the Alzheimer’s Association International Conference (AAIC) has demonstrated how a blood-based biomarker test can improve the accuracy of Alzheimer’s disease diagnosis, by detecting Alzheimer's disease pathology.
Gold standard diagnostic tests for Alzheimer’s disease pathology include PET scans and analyses of cerebrospinal fluid taken from lumbar punctures. These tests directly detect the presence of amyloid plaques in the brain, but can be costly and invasive. As a result, the last decade has seen increasing interest and investment in research on blood-based biomarkers, measurable proteins in the blood which can indicate the presence of Alzheimer’s disease pathology in the brain. In their new study, a team of researchers led by Oskar Hansson and Sebastian Palmqvist (Lund University, Sweden) evaluated the accuracy of a blood-based biomarker test for Alzheimer’s disease pathology, showing how it could improve the accuracy of diagnosis in primary and secondary care.
The researchers analysed blood samples from 1,213 patients with cognitive complaints who were undergoing evaluation in Swedish primary care clinics (515 patients) or memory clinics (698 patients). The tests were carried out in two ways: a first set of samples was analysed in a single batch, and a second set of samples was analysed prospectively, with samples sent individually for analysis within 2 weeks of collection. This mimics the way samples are analysed in real-world clinics. The study used a test from C2N Diagnostics called PrecivityAD2, which performs mass spectrometry to calculate the ratios of two proteins: tau217 (phosphorylated and total tau217) and amyloid beta (amyloid beta-40 and amyloid beta-42). Based on these test results, an Amyloid Probability Score is computed (termed the APS2 score) which indicates the likelihood of an individual having Alzheimer’s disease pathology in the brain. APS2 results were compared to CSF or amyloid PET analysis, and clinicians in primary or secondary care were also asked if they thought patients had Alzheimer’s disease, based on clinical examination, cognitive testing and a CT scan.
The results of the study showed that the PrecivityAD2 test had a diagnostic accuracy of 91% in the memory clinic cohort, and 89% in the primary care cohort. This did not differ substantially when samples were analysed in a single batch or prospectively. In comparison, primary care clinicians had an overall diagnostic accuracy of 58%, when looking for Alzheimer’s pathology in the brain, with a diagnostic confidence of 5.8 (on a scale of 0-10, 10 being the highest level of confidence). Memory clinic specialists had an overall diagnostic accuracy of 71%, with an average diagnostic confidence of 6 on a scale of 0-10. According to Sebastian Palmqvist, the first author of the study, this underscores the lack of good, cost-effective diagnostic tools, particularly in primary care, and indicates the potential improvement in diagnosis with the adoption of this blood test in healthcare settings.
Read the JAMA publication: https://jamanetwork.com/journals/jama/fullarticle/2821669