The fully human monoclonal antibody gantenerumab, which targets amyloid-β plaques, seems to cause a dose-dependent decrease in brain amyloid levels, according to a clinical trial involving 18 patients with mild to moderate Alzheimer disease (AD).

Accumulation of toxic amyloid plaques is a hallmark of the AD brain, and targeting of this process is a therapeutic strategy under investigation. In the current multicenter study, published in Archives of Neurology, patients were randomly assigned to receive placebo or monthly intravenous doses of gantenerumab (60 mg or 200 mg), which were administered for 2–7 months. PET scanning for the tracer carbon-11-labeled Pittsburgh compound B (11C-PIB) was performed to measure regional brain amyloid levels at baseline and at the end of treatment.

Patients in the placebo group (n = 4) showed a mean 11% increase in cortical 11C-PIB signal during the study. By contrast, the signal increased by an average of only 2.1% in patients receiving 60 mg gantenerumab (n = 6), and declined by 9.4% in patients in the 200-mg group (n = 6). The therapeutic antibody seems, therefore, to produce a dose-dependent reduction in plaque burden, although the small sample sizes preclude firm conclusions from being drawn.

In an ex vivo phagocytosis assay, live-cell imaging revealed that the drug dose-dependently increased microglial uptake of amyloid plaques within hours.

Future research should address whether targeting of amyloid levels translates into clinical benefit, and whether mild to moderate AD is a sufficiently early time point for starting treatment.