Biomarker Heterogeneity in Patients Receiving Lecanemab in the Real World

BackgroundWhile amyloid-{beta} (A{beta}) biomarker positivity is sufficient before initiating anti-A{beta} antibody therapy, recent revised criteria also highlight the importance of other biomarkers (ATNIVS) to understand heterogeneity in AD. Design, Setting, and ParticipantsWe reviewed patients who attended our specialty clinic between December 2023 and October 2024. Some participated in tau PET study (18F-MK6240). MRI was assessed using Fazekas score. Remaining samples were analyzed for plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and CSF -synuclein seed amplification assay (SAA). ResultsDuring the period, 200 attended and 147 proceeded to screening. Lecanemab was started in 93 of 108 A+ patients; mean age 74.2 years, 73.1% female. While all tested started on lecanemab were positive on amyloid PET, 21% had only regional positivity with lower A{beta} burden (centiloid 31.3 {+/-}17.5 vs 67.6 {+/-}20.2) and higher age (79.2 {+/-}5.1 vs 73.3 {+/-}8.9). While all tested had CSF A{beta}42/40 values below the single cut-off 0.067 in Japan, three (8.6%) had values close to the cutoff (0.059-0.067), all of whom were all male. Other biomarkers also widely varied from normal to fully abnormal; CSF pTau181 (40.5-168 pg/mL, cut-off 56.5), tau PET-based Braak stage (0-VI), NfL (10.0-103.3 pg/mL), GFAP (121.9-652.5 pg/mL), Fazekas score (0-3), and positive -synuclein SAA (25-33%). Some associations were indicated including higher Fazekas scores in amyloid PET regional-positive group and higher plasma NfL in CSF A{beta}42/40 0.059-0.067 group. ConclusionsWe identified substantial heterogeneity in ATNIVS biomarker profiles among patients receiving lecanemab in a real-world setting.