Cerebrospinal Fluid Biomarker Measurement

IgG and albumin concentrations were measured by immunoturbidimetry on a Cobas instrument (Roche Diagnostics). The IgG index and albumin ratio were calculated as previously described.^{19 (link)} Cerebrospinal fluid neopterin was measured using a commercially available immunoassay (Brahms).^{20 (link)} Cerebrospinal fluid β₂-microglobulin (β₂M) was measured using the N latex β₂M kit on the Atellica NEPH 630 System (Siemens Healthcare GmbH). The CSF NfL was measured using a previously described in-house sandwich enzyme-linked immunosorbent assay.^{21 (link)} The NfL concentrations were age adjusted and reported as the equivalent for 65 years of age as previously described.^{22 (link)} The CSF glial fibrillary acidic protein concentration was measured using an in-house enzyme-linked immunosorbent assay as previously described.^{23 (link)} Cytokine concentrations were measured using the novel S-PLEX Proinflammatory Panel I. The S-PLEX format provides signal enhancement that achieves sensitivity in femtograms per milliliters (eMethods in the Supplement). The CSF and plasma samples were tested undiluted.