In a recent study published in The Journal of the American Medical Association, a team of researchers in Sweden examined whether the ratio of phosphorylated tau 217 protein to non-phosphorylated tau 217 protein in plasma, determined through a blood test could be combined with the amyloid probability score 2 (APS2) and be used in primary and secondary care facilities to accurately diagnose Alzheimer's disease and lower the misdiagnosis rates for the disease.
Study: Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care. Image Credit: Andrii Vodolazhskyi / Shutterstock
Background
Research indicates that 20% of women and 10% of men develop Alzheimer's disease-related dementia. Individuals exhibiting the early symptoms of cognitive deficits visit primary care facilities, but a very small portion of those patients are referred further to secondary care centers. The rate of misdiagnoses of symptomatic Alzheimer's disease is between 25% and 35% or even more among patients treated at primary care centers.
Specialized tests, such as cerebrospinal fluid assessments for Alzheimer's disease markers and positron emission tomography (PET) scans, can lower misdiagnosis rates. Furthermore, the treatment of early symptomatic Alzheimer's disease with anti-amyloid immunotherapies has been approved, but positive biomarker tests are required to initiate treatment. However, many primary and secondary care centers lack the facilities for reliable biomarker-based diagnoses or specialized tests.
About the study
In the present study, the researchers examined whether the use of the ratio of phosphorylated tau 217 (p-tau217) protein to non-phosphorylated tau 217 protein in plasma, which is expressed as a percentage of p-tau217, can be used as an accurate biomarker in combination with the amyloid probability score 2 to reliably diagnose Alzheimer's disease without the need for specialized tests such as PET scans and cerebrospinal fluid analyses.
Studies have found that p-tau217 in plasma is indicative of cerebrospinal fluid-linked Alzheimer's disease pathology, PET scan measured Alzheimer's biomarkers and the neuropathological changes that occur in Alzheimer's patients.
If the ratio of p-tau217 to non-p-tau217 can be combined with the existing biomarker of amyloid probability score 2, which is the ratio of amyloid-β 42 (Aβ42) and amyloid-β 40 (Aβ40) to provide an accurate blood test-based biomarker for reliably diagnosing Alzheimer's disease in primary and secondary care stages, it could help significantly reduce the rate of misdiagnoses.
To validate the use of p-tau217 ratio in plasma as a biomarker, the researchers used predefined cutoff values for biomarkers and examined the effectiveness of p-tau217 plasma percentage by itself and in combination with Aβ42: Aβ40 in diagnosing clinical Alzheimer's disease or Alzheimer's disease pathology in individuals exhibiting early cognitive symptoms.
They also evaluated how accurate the blood biomarkers were in diagnosing Alzheimer's disease when analyzed in biweekly batches and compared their accuracy with that of dementia specialists and primary healthcare physicians.
The study's secondary objectives were to examine how the blood biomarkers performed at different stages of cognitive decline and to analyze different approaches to cutoff values for the blood test.
Patients exhibiting mild cognitive impairment, subjective decline in cognition, or dementia were recruited into primary and secondary care cohorts for single-batch analysis and prospective analysis of biweekly batches. The participants underwent assessments from dementia specialists and physicians using standard evaluation methods.
Plasma samples obtained from the participants were analyzed using mass spectrometry for the amyloid beta and tau protein markers. Additionally, cerebrospinal fluid samples were obtained and analyzed for amyloid beta biomarkers.
Results
The study found that using a predefined cutoff value for biomarkers and a combination of percentage p-tau217 and Aβ42: Aβ40 in plasma samples provided highly accurate diagnoses of Alzheimer's disease pathology. Furthermore, the performance of Aβ42: Aβ40 as a biomarker was consistent across the biweekly analyses of plasma samples, indicating that the assay performance was robust.
Despite variations in clinical and demographic characteristics of patients between the primary and secondary care cohorts, the performance of the blood biomarkers was comparable across cohorts. Additionally, the blood test demonstrated diagnostic accuracy greater than not only that of physicians in primary care centers but also that of dementia specialists.
Moreover, although the rate of comorbidities such as kidney disease was high in the study population, the performance of the blood test biomarkers in accurately detecting Alzheimer's disease pathology was high.
Conclusions
Overall, the study showed that the use of a combination of percentage p-tau217 and Aβ42: Aβ40 as biomarkers, detected from plasma samples, provided a highly accurate and reliable method to diagnose Alzheimer's disease pathology among patients exhibiting dementia or mild cognitive impairments.
The use of plasma samples for this method, without the need for specialized tests such as PET scans, could potentially increase the detection of Alzheimer's disease in both primary and secondary care facilities and lower the misdiagnosis rates.
Journal reference:
- Palmqvist, S., Tideman, P., Mattsson-Carlgren, N., Schindler, S. E., Smith, R., Ossenkoppele, R., Calling, S., West, T., Monane, M., Verghese, P. B., Braunstein, J. B., Blennow, K., Janelidze, S., Stomrud, E., Salvadó, G., & Hansson, O. (2024). Blood biomarkers to detect Alzheimer disease in primary care and secondary care. JAMA. DOI:10.1001/jama.2024.13855, https://jamanetwork.com/journals/jama/fullarticle/2821669
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