Performance of blood biomarkers in internal jugular vein for Alzheimer disease pathologies: the Delta Study

BackgroundSystemic factors confound blood tests for the diagnosis of Alzheimer disease (AD). The Delta study explored whether blood biomarkers from the vein proximal to the brain perform better in detecting cerebral AD pathologies. MethodsBlood was collected from the internal jugular vein (IJV) and median cubital vein (MCV) in the discovery (n=371) and validation (n=92) cohorts. AD biomarkers were measured with Lumipulse G and Simoa methods. A{beta} and tau PET imaging and cerebrospinal fluid (CSF) biomarkers were used to evaluate brain pathologies. ResultsThe levels of A{beta}42, A{beta}40, p-tau217, p-tau181, GFAP and NfL were higher in the IJV than MCV and highly correlated between the two sites. IJV-A{beta}42/40 had stronger correlations with A{beta} PET Centiloids and tau PET meta-temporal SUVR than MCV-A{beta}42/40. In detecting cerebral A{beta} positivity, IJV-A{beta}42/40 demonstrated a significantly higher accuracy (79.9% to 92.9% vs. 72.4% to 88.8%) and a lower percentage of uncertain individuals (17.8% to 54.5% vs. 31.3% to 70.1%) than MCV-A{beta}42/40. Moreover, the diagnostic accuracy of Lumipulse G IJV-A{beta}42/40 (88.2% to 92.9%) was statistically equivalent to that of MCV-p-tau217 (90.2% to 94.3%), although the intermediate percentage of IJV-A{beta}42/40 was higher (17.8% to 34.0% vs. 0.7% to 17.5%) than MCV-p-tau217. These findings were verified in the validation cohort. DiscussionIJV-A{beta}42/40 performs better than MCV-A{beta}42/40 in detecting cerebral AD pathologies, offering a novel perspective to reduce the impacts of systemic factors and comorbidities on blood tests.