CSF and plasma biomarkers for DLB

AbstractBackgroundCSF biomarkers of amyloid and tau provide components of the A/T/N classification for AD and hold clinical prognostic value. They can help to identify how AD co‐pathology contributes to DLB. Alpha‐synuclein (a‐Syn) aggregation is a key pathogenic process in DLB, proposed to follow a staging system for spread of pathology. We review existing CSF markers in DLB and evaluate how well RT‐QuIC, a protein misfolding amplification assay for a‐Syn, detects DLB and different degrees of a‐Syn pathology at autopsy, and performs in RBD, a prodromal stage of DLB. We discuss the potential for plasma biomarkers for diagnosis and progression in DLB.Method1) selected studies of CSF biomarker data from RBD subjects and from published data for DLB on A/T/N biomarkers and on a‐Syn RT‐QuIC and other a‐Syn biomarkers; 2) analysis of different parameters of a‐synuclein RT‐QuIC and clinical‐pathological correlations for RT‐QuIC; 3) data on plasma neurofilament light as a progression biomarker.Result1) AD biomarkers in CSF support AD co‐pathology in a substantial percentage of cases of DLB, which is associated with faster cognitive progression. Data on RBD and prodromal DLB are limited. 2) RT‐QUiC has high sensitivity and specificity for PD and DLB diagnosis, including RBD. RT‐QuIC parameters (time to 50% of maximal fluorescence or peak fluorescence) do not correlate with measures of movement or cognition. Limiting dilution may provide an index of seeding burden, but in preliminary analyses shows a weak relationship to clinical progression; 3) longitudinal Nfl plasma levels in the PPMI cohort show a slight increase in early PD and RBD, to a greater extent than in aging alone, with much overlap. Concomitant AD pathology may drive plasma Nfl changes.ConclusionCSF biomarkers related to neurodegeneration may provide value in early DLB. CSF Aβ1‐42/Tau has prognostic value for cognitive decline in DLB. RT‐QuIC for a‐synuclein in CSF has diagnostic but not predictive value. Plasma biomarkers for diagnosis of pathology are emerging, but prognostic markers will need extensive additional research.