ATNIVS biomarker heterogeneity in real-world patients receiving lecanemab.

BACKGROUND: While amyloid-β (Aβ) biomarker positivity is sufficient before initiating anti-Aβ antibody therapy, recent revised criteria also highlight the importance of other biomarkers (ATNIVS) to understand heterogeneity in AD. DESIGN, SETTING, AND PARTICIPANTS: We 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 α-synuclein seed amplification assay (SAA). RESULTS: During 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 Aβ 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 Aβ42/40 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 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 α-synuclein SAA (25-33%). Some associations were indicated including higher Fazekas scores in amyloid PET regional-positive group and higher plasma NfL in CSF Aβ42/40 0.059-0.067 group. CONCLUSIONS: We identified substantial heterogeneity in ATNIVS biomarker profiles among patients receiving lecanemab in a real-world setting.