A longitudinal cohort study published in The Lancet Neurology and using Alamar Biosciences (Nasdaq: ALMR) proteomics technology has found that patients with early symptomatic Alzheimer's disease exhibit different biological responses during treatment with lecanemab (Leqembi; Eli Lilly), with proteins associated with amyloid clearance differing from those associated with subsequent cognitive decline.
The study, led by investigators at Washington University School of Medicine in St. Louis, profiled 2,385 plasma samples from 1,967 participants, including 197 patients receiving lecanemab as part of standard clinical care, alongside untreated comparison groups drawn from the Knight Alzheimer Disease Research Center.
Researchers used Alamar’s NULISAseq CNS 120 panel to measure 130 proteins associated with amyloid and tau pathology, inflammation, neurodegeneration, and synaptic function. Among lecanemab-treated patients, 34 biomarkers changed significantly with the number of infusions received.
The biomarkers did not move uniformly. Several markers associated with Alzheimer’s pathology, including phosphorylated tau species, MAPT, GFAP, and BACE1, shifted toward levels observed in amyloid-negative controls during treatment, while other proteins followed different trajectories. The investigators reported that biomarker patterns linked to amyloid removal were largely distinct from those associated with cognitive decline, suggesting that the biological response to plaque clearance does not fully capture the processes underlying clinical progression.
Among the proteins most strongly distinguishing treated patients from controls, brain-derived forms of tau consistently outperformed the same proteins circulating in the periphery, accounting for four of the top five both before treatment and at the last infusion stage. The study's authors said that amyloid clearance and cognitive response reflect different biological processes, which they reported helps explain why clearing amyloid does not produce the same degree of clinical benefit in every patient — a pattern observed both in this cohort and across anti-amyloid trials.