Published on: Nov 11, 2025
A research team from Osaka Metropolitan University in Japan, led by graduate student Tatsushi Oura and Dr. Hiroyuki Tatekawa, has discovered that treatment with the anti-amyloid drug lecanemab—designed to remove amyloid plaques from the brain—does not improve the brain’s waste clearance function in Alzheimer’s disease (AD) patients over the short term.
The findings suggest that even after successful plaque removal, neuronal damage and impaired waste clearance remain, indicating that these deficits may be too advanced to recover quickly. This highlights the complex nature of Alzheimer’s disease and the importance of addressing multiple pathological pathways simultaneously.
Alzheimer’s disease, the most common neurodegenerative disorder, remains difficult to treat due to its multifactorial origins. One well-known driver of neuronal injury is the buildup of the protein amyloid-β (Aβ). In healthy brains, the glymphatic system circulates cerebrospinal fluid through brain tissue to clear metabolic waste like Aβ. However, in AD patients, amyloid buildup stiffens arteries and disrupts this flow, triggering neurodegeneration and cognitive decline.
Lecanemab, a recently approved therapy, is known to reduce accumulated Aβ. To assess its broader impact, the Osaka team evaluated the glymphatic function of patients before and three months after lecanemab treatment using the DTI-ALPS index, a neuroimaging marker of waste clearance efficiency.
Contrary to expectations, the study found no significant change in the index after treatment. The results indicate that while lecanemab effectively reduces amyloid plaques and may slow cognitive decline, it may not be sufficient to restore lost clearance function in the short term. This suggests that by the time symptoms appear, neuronal and clearance system damage may already be deeply entrenched.
Even when Aβ is reduced by lecanemab, impairment of the glymphatic system may not recover within the short term, Oura explained. In the future, we aim to study factors such as age, disease stage, and white matter lesions to better understand how changes in the glymphatic system relate to treatment outcomes. This will help us determine the most effective ways to administer therapy.
The study underscores the need for multi-targeted approaches in Alzheimer’s treatment—beyond plaque clearance—to promote overall brain health and functional recovery.
Source: https://www.omu.ac.jp/en/info/research-news/entry-95626.html
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