Clinical utility of cerebrospinal fluid biomarkers measured by LUMIPULSE (R) system

Objectives: Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) are well-established in research settings, but their use in routine clinical practice remains a largely unexploited potential. Here, we examined the relationship between CSF biomarkers, measured by a fully automated immunoassay platform, and brain beta-amyloid (A beta) deposition status confirmed by amyloid positron emission tomography (PET). Methods: One hundred ninety-nine CSF samples from clinically diagnosed AD patients enrolled in a clinical study and who underwent amyloid PET were used for the measurement of CSF biomarkers A beta 1-40 (A beta 40), A beta 1-42 (A beta 42), total tau (t-Tau), and phosphorylated tau-181 (p-Tau181) using the LUMIPULSE system. These biomarkers and their combinations were compared to amyloid PET classification (negative or positive) using visual read assessments. Several combinations were also analyzed with a multivariable logistic regression model. Results: A beta 42, t-Tau, and p-Tau181, and the ratios of A beta 42 with other biomarkers had a good diagnostic agreement with amyloid PET imaging. The multivariable logistic regression analysis showed that amyloid PET status was associated with A beta 40 and A beta 42, but other factors, such as MMSE, sex, t-Tau, and p-Tau181, did not significantly add information to the model. Conclusions: CSF biomarkers measured with the LUMIPULSE system showed good agreement with amyloid PET imaging. The ratio of A beta 42 with the other analyzed biomarkers showed a higher correlation with amyloid PET than A beta 42 alone, suggesting that the combinations of biomarkers could be useful in the diagnostic assessment in clinical research and potentially in routine clinical practice.