Evaluating the Utility of Existing Plasma Biomarkers in a Clinical Patient Cohort

Abstract

AbstractBackgroundBiomarker assessments will become an instrumental component of effective clinical management and trial coordination for Alzheimer’s Disease (AD) and related dementias and will enable precision medicine approaches to diagnosis and treatment. Plasma offers an inexpensive non‐invasive peripheral biofluid for biomarker assessments that can easily be collected longitudinally. The development of ultrasensitive single molecule array (SIMOA) assays has enabled plasma measurements for AD‐related blood biomarkers. Indeed, several plasma biomarkers were recently identified as potentially useful for AD and related dementias. However, their utility in additional clinical cohorts requires further investigation.MethodsPlasma samples were collected from participants clinically diagnosed as cognitively unimpaired (CU; n=30), mild cognitive impairment (MCI; n=60) or probable AD (AD; n=34) from the Michigan ADRC. Levels of total Tau, phospho‐tau 181 (pT181), amyloid β40 (Aβ40), and amyloid β42 (Aβ42) were measured using SIMOA. Ongoing studies will include additional samples and measure plasma neurofilament light chain, glial fibrillary acidic protein, placental growth factor, vascular endothelial growth factor, and phospho‐tau 231. Biomarker levels were compared across diagnostic groups and correlated with cognitive and demographic variables.ResultsAmong the biomarkers assessed, interim results indicated significantly elevated pTau181 in AD compared to CU and receiver operating characteristic (ROC) analysis showed an AUC of 0.81 for CU versus AD. This analyte correlated significantly with CDR sum of boxes (p=0.01). There was a nonsignificant reduction (8%) in the Aβ42:Aβ40 ratio and an AUC of 0.65 for CU versus AD. Aβ40 and the Aβ42:Aβ40 ratio were significantly correlated with age. No sex differences were detected. Except for pTau181, no significant correlations with CDR sum of boxes or CDR global were found. Biomarker levels showed no correlation with body mass index (BMI) within diagnostic groups.ConclusionsGenerally, our results align fairly well with other studies using clinical patient cohorts with extensive additional biomarkers (e.g. PET tracer measurements and CSF biomarkers). The AD‐associated increase in plasma pT181 levels support the potential utility of this form of phospho‐tau as a useful plasma biomarker. The lack of significant effects with the other biomarkers used here suggests additional novel biomarkers are necessary.