ATNIVS biomarker heterogeneity in real-world patients receiving lecanemab - PubMed

7 hours ago

Amyloid-β (Aβ) biomarker positivity is necessary for starting lecanemab therapy, but ATNIVS biomarkers (including tau, neurodegeneration, inflammation, vascular, and α-synuclein) show significant heterogeneity in real-world Alzheimer's disease patients.
In a study of 93 patients starting lecanemab (mean age 74.2, 73.1% female), all were amyloid PET positive, but 21% had only regional positivity with lower Aβ burden and older age compared to those with more widespread positivity.
CSF Aβ42/40 ratios were all below the cut-off in Japan, but 8.6% (all male) had values close to the threshold, indicating variability even among those eligible for treatment.
Other biomarkers exhibited wide ranges: CSF pTau181, tau PET Braak stages (0-VI), plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), Fazekas scores (0-3), and positive α-synuclein seed amplification assay results (25-33%).
Associations noted included higher Fazekas scores in the amyloid PET regional-positive group and higher plasma NfL in patients with CSF Aβ42/40 ratios of 0.059-0.067, suggesting links between vascular changes, neurodegeneration, and amyloid levels.
The findings underscore substantial biomarker heterogeneity in real-world patients receiving lecanemab, highlighting the complexity of Alzheimer's disease and the need for comprehensive biomarker profiling in clinical practice.

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