Researchers at Osaka Metropolitan University report that while the Alzheimer’s drug lecanemab reduces amyloid plaques, MRI measures found no improvement in the brain’s glymphatic waste-clearance three months after treatment began, underscoring the disease’s complexity and the need for multi-target approaches.
A team led by graduate student Tatsushi Oura and Dr. Hiroyuki Tatekawa at Osaka Metropolitan University examined whether lecanemab’s plaque-clearing effect translates into early recovery of the brain’s waste-removal function. Using diffusion tensor imaging along the perivascular space (DTI-ALPS)—an MRI-derived index linked to glymphatic activity—the researchers scanned patients before starting lecanemab and again at three months. In this preliminary cohort (n=13), they found no significant change in the DTI-ALPS index between baseline and the three‑month follow‑up, indicating no short‑term recovery of the glymphatic system.
“The impairment of the glymphatic system may not recover within the short-term, even when Aβ is reduced by lecanemab,” Oura said. The findings were published online in the Journal of Magnetic Resonance Imaging in September 2025.
The glymphatic system helps clear metabolic waste, including amyloid‑β, from brain tissue. Although lecanemab is an FDA‑approved treatment for early Alzheimer’s disease that reduces amyloid plaques—and has been shown in a phase 3 trial to slow clinical decline—this study suggests that early neuronal injury and clearance deficits may already be established by symptom onset and are not quickly reversed by amyloid removal alone.
According to the university, future work will assess how factors such as patient age, disease stage, and the burden of white‑matter lesions relate to treatment response and may inform how best to administer therapy over longer time frames.
