Background:While amyloid-β (Aβ) biomarker positivity is sufficient before initiating anti-Aβ antibodytherapy, recent revised criteria also highlight the importance of other biomarkers (ATNIVS) tounderstand heterogeneity in AD.

Methods: We reviewed patients who attended our specialty clinic between December 2023 andOctober 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 acidicprotein (GFAP), and CSF α-synuclein seed amplification assay (SAA).

Results:During the period, 200 attended and 147 proceeded to screening. Lecanemab was started in93 of 108 A+ patients; mean age 74.2 years, 73.1% female. While all tested started on lecanemab werepositive on amyloid PET, 21% had only regional positivity with lower Aβ burden (centiloid 31.3±17.5 vs67.6±20.2) and higher age (79.2 ±5.1 vs 73.3 ±8.9). While all tested had CSF Aβ42/40 values below thesingle cut-off 0.067 in Japan, three (8.6%) had values close to the cutoff (0.059-0.067), all of whom weremale. Other biomarkers also widely varied from normal to fully abnormal; CSF pTau181 (40.5-168pg/mL, cut-off 56.5), tau PET-based Braak stage (0-VI), NfL (10.0-103.3 pg/mL), GFAP (121.9-652.5pg/mL), Fazekas score (0-3), and positive α-synuclein SAA (25-33%). Some associations were indicatedincluding higher Fazekas scores in amyloid PET regional-positive group and higher plasma NfL in CSFAβ42/40 0.059-0.067 group.

Conclusion: We identified substantial heterogeneity in ATNIVS biomarker profiles among patientsreceiving lecanemab in a real-world setting.

Keywords: Alzheimer’s diseaseLecanemabATNIVS biomarkersAmyloid-βTau pathologyReal-world studyBiomarker heterogeneityAmyloid PETCerebrospinal fluid biomarkersα-synuclein co-pathology

Full Publication: https://doi.org/10.1016/j.tjpad.2026.100567