Innovative blood tests may replace spinal taps in AD

New blood tests for Alzheimer's disease demonstrate high accuracy in detecting disease biomarkers. This reduces the need for invasive spinal taps by more than 50%.

study: Clinical performance of a fully automated Lumipulse plasma P-TAU217 assay in mild cognitive impairment and mild dementia. Image credit: pickadook/shutterstock.com

The fully automated Lumipulse plasma phosphorylation Tau 217 (P-TAU217) assay has the potential to effectively diagnose mild cognitive impairment (MCI) and mild dementia. recently Alzheimer's disease and dementia Researchers have shown that this method can potentially reduce more than 50% of lumbar punctures performed for diagnostic purposes.

How is Alzheimer's disease diagnosed?

The clinical diagnosis of Alzheimer's disease (AD) is based on the detection of amyloid beta (Aβ) and tau (T) proteins as biomarkers for cerebrospinal fluid (CSF) and positron emission tomography (PET). The rapid progression of neurodegenerative diseases such as AD highlights the need to establish Aβ positivity before anti-amyloid immunotherapy is initiated.

Previous studies highlight the greater benefits associated with blood-based biomarkers (BBMS) compared to CSF ​​and PET for AD diagnosis. For example, blood sampling improves the ease of recruitment, diagnosis, and monitoring AD progression, while CSF sampling involves invasive lumbar puncture (LP), which increases the risk of bleeding, infection, and nerve damage. Included.

Of all BBMs, P-TAU217 may distinguish AD from other neurodegenerative diseases through its significant changes and may track cortical atrophy worsens over time. Mass spectrometry is used to quantify low-resistant plasma proteins, but new automated immunoassay techniques are required to accurately determine plasma P-TAU217 and Aβ pathology.

Previous studies have confirmed the usefulness of fully automated methods such as Fujirebio Lumipulse in diagnostic laboratories to reduce the variability in assay performance. However, the effectiveness of these assays must be verified through actual clinical data.

About the research

The current study included a fully automated Fujitsu research scope of use (RUO) to determine CSF-defined Aβ pathology of individuals undergoing lumbar puncture (LP) for disease diagnosis in local experts' special memory. ) We investigated the performance of the Lumipulse G plasma P-TAU217 assay. Clinic (RSMC).

RSMC conducts detailed cognitive/medical assessments, neuroimaging, and routine laboratory surveys on 400-500 individuals each year. If necessary, patients undergo CSF ​​tests to detect AD pathology.

A standard curve and supplied calibrator was used for optimal assay performance of the Lumipulse G600 II analyzer. Six plasma samples were analyzed twice over two days to estimate interassay coefficient of variation (CV).

Survey results

A total of 148 participants were recruited for the current study, of which 54.1% were women with an average age of 69.4 years. Approximately 68% of participants were diagnosed with MCI, while 31% had mild dementia. The average time from initial diagnosis to confirmation was approximately 120 days.

In the CSF test, 60.8% of the study cohort were estimated to be Aβ positive. The pathogenesis of Aβ-negative individuals was Lewy's body disease, frontotemporal dementia, and vascular cognitive impairment. In some individuals who were negative for Aβ, the neurodegenerative pathogenesis was not clear after diagnostic testing. However, each of these study participants was diagnosed with MCI.

Plasma sample analysis using the Lumipulse P-Tau217 assay revealed that the median plasma P-TAU217 values ​​was four times higher in Aβ-positive study participants than in Aβ-negative individuals. Plasma P-TAU217 had an area under curve (AUC) value of 0.92 in Aβ-positive patients.

In theory, a two-family approach was used to provide a more stringent threshold. In the current analysis, 90%, 95%, and 97.5% of the sensitivity/specificity thresholds for plasma P-TAU217 may have avoided the need for more than half of the LP.

Fewer false positive results were generated with 90% specificity. These individuals had MCI without a specific neurodegenerative pathogenesis.

Conclusion

The current study confirmed the excellent performance of a fully automated Lumipurus assay in detecting Aβ positives in actual clinical cohorts of patients diagnosed with MCI and mild dementia. Taken together, these findings indicate that this device can be used in laboratory settings for diagnostic purposes with higher specificity and sensitivity than current analytical approaches.

In the future, the potential effects of renal function and vascular risk factors on plasma P-TAU217 performance should be assessed using larger and more diverse samples.