Alamar Biosciences Study in Lancet Neurology Reveals Lecanemab Responses

Plasma Biomarkers Tracked During Lecanemab Treatment

The study utilized Alamar’s NULISAseq™ CNS 120 panel to measure 130 plasma proteins spanning amyloid pathology, tau pathology, inflammation, neurodegeneration, and synaptic function. Researchers profiled 2,385 samples collected from 1,967 participants, using 25 microliters of plasma per sample. The participants included individuals receiving lecanemab as part of standard clinical care at the Washington University Memory Diagnostic Center alongside untreated comparison groups from the Knight Alzheimer Disease Research Center.

Carlos Cruchaga, PhD, Professor of Psychiatry and director of the NeuroGenomics and Informatics Center at Washington University School of Medicine, noted the shift in clinical visibility. Anti-amyloid therapies are now part of routine care, but until now clinicians have had a narrow window into the underlying biological activity, according to Cruchaga, who served as co-senior author of the study.

Our findings show that Alzheimer’s disease and neurodegeneration biomarkers have unique trajectories that capture specific biological process associated with treatment response.

Carlos Cruchaga, Washington University School of Medicine

Divergent Biological Pathways of Amyloid Clearance and Cognition

The data revealed that proteins associated with amyloid clearance were largely separate from those linked to subsequent cognitive decline. This divergence demonstrates that amyloid clearance and cognitive response reflect distinct biological processes. Researchers indicated this separation helps explain why clearing amyloid does not yield the exact same degree of clinical benefit in every patient, a pattern observed both in this cohort and across broader anti-amyloid clinical trials.

Among 197 patients treated with lecanemab specifically, 34 of the 130 biomarkers changed significantly relative to the number of infusions received, though these proteins did not all move in the same direction. Brain-derived forms of tau consistently outperformed peripheral circulating variants when distinguishing treated patients from controls, accounting for four of the top five biomarkers both prior to treatment and at the final infusion stage.

Implications of Ultra-High Sensitivity Precision Proteomics

Differentiating brain-derived tau from its systemic counterpart demands high specificity and extreme sensitivity to detect very low concentrations in blood. Tracking these variants alongside more than 100 additional proteins in a single assay enabled the research team to monitor pathology and treatment response simultaneously.

Yuling Luo, PhD, founder, CEO, and chair of Alamar Biosciences, emphasized the limitations of single-marker approaches in modern neurology.

This study shows why measuring one or two biomarkers is not enough to understand what is happening during treatment and why ultra-high sensitivity matters. Alamar’s precision proteomics platform gives researchers a much richer picture of treatment response and helps us understand why patients with the same diagnosis can have very different outcomes.

Yuling Luo, Alamar Biosciences