Alzheimer’s Drug Reduces Amyloid but Fails to Restore Brain Waste Flow

 

Whoops, lecanemab is not for me. With my damaged brain already running with millions to billions less neurons I'll pass on more brain shrinkage. But I'm not medically trained so don't listen to me.

From this article comes the following paragraphs:

YIKES! FDA Approves Lecanemab Against Alzheimer’s

But there is a new and disturbing fly in the ointment.. A study published in the journal Neurology (March 27, 2023) reveals that anti-amyloid drugs like lecanemab can cause brain shrinkage. The researchers call this accelerated “brain atrophy.” 

Alzheimer’s Drug Reduces Amyloid but Fails to Restore Brain Waste Flow

Summary: Researchers found that lecanemab, the Alzheimer’s drug designed to clear amyloid-β plaques, does not improve the brain’s waste clearance system in the short term. In a three-month study using MRI-based DTI-ALPS imaging, scientists observed no measurable recovery in glymphatic function after treatment.

This suggests that once neuronal and clearance system damage occurs, it may be too advanced to reverse quickly. The results emphasize the need for multi-targeted strategies to address Alzheimer’s disease beyond amyloid reduction alone.

Key Facts

• Study Finding: Lecanemab reduces amyloid-β but doesn’t restore glymphatic waste clearance after 3 months.
• Implication: Short-term therapy may not repair established neuronal damage in Alzheimer’s.
• Future Direction: Research will assess long-term effects and age-related factors influencing treatment outcomes.

Source: Osaka Metropolitan University

A group from Osaka Metropolitan University in Japan, led by graduate student Tatsushi Oura and Dr. Hiroyuki Tatekawa, found that treatment using the drug lecanemab to remove amyloid plaques in the brain does not change the waste clearance function in the brains of Alzheimer’s disease (AD) patients in the short term.

This suggests that even after treatment, the AD patients’ nerves are already damaged, and the waste clearance function does not recover in the short term. Their findings show the complexity of the disease and the need to address multiple disease-causing pathways simultaneously in the future.

Their findings add to the complicated process of unraveling AD’s mechanisms. Despite being the most common form of neurodegenerative disease, it is tricky to treat because of its multiple causes.

One cause of the nervous damage common in AD is the accumulation of the protein amyloid-β (Aβ) in the brain. In healthy patients, the glymphatic system moves cerebrospinal fluid along the spaces around the arteries into the brain tissue, where it mixes with interstitial fluid to carry away metabolic waste like Aβ. This is called the ‘glymphatic system’ after the glial cells involved in the process.

However, in AD patients, Aβ builds up, stiffening arteries and reducing the flow from the brain to the cerebrospinal fluid. This blockage triggers a chain of neurodegenerative processes, leading to AD symptoms.

The recently approved therapeutic lecanemab reduces accumulated Aβ. The team from the university’s Graduate School of Medicine evaluated the glymphatic system before and after treatment in patients who received lecanemab therapy, using the DTI-ALPS index.

Contrary to expectations, they found no significant change in the index between pre-treatment and 3 months after treatment.

They concluded that although anti-amyloid therapy can reduce plaque burden and slow further cognitive worsening, it may be insufficient to restore lost function. This suggests that neuronal damage and clearance system deficits have already been well established by the time the patient starts showing symptoms. Their findings show the range of factors involved in the progression of AD, many of which are not easily reversible.

“Even when Aβ is reduced by lecanemab, impairment of the glymphatic system may not recover within the short-term,” Oura said.

“In the future, we want to look at factors like age, the stage of the disease, and degree of lesions in the white matter to further understand the relationship between changes in the glymphatic system due to lecanemab treatment and the outcome of treatment. This will help understand the best way to administer treatment to patients.”

Funding: This study was supported by the Takeda Science Foundation (ROR ID: 02y123g31) and Japan Society for the Promotion of Science (JSPS) KAKENHI (grant number: 25K19115). Data were obtained from the OASIS (OASIS-3, Longitudinal Multimodal Neuroimaging: Principal Investigators: T. Benzinger, D. Marcus, and J. Morris, supported by NIH Grants: NIH P30 AG066444, P50 AG00561, P30 NS09857781, P01 AG026276, P01 AG003991, R01 AG043434, UL1 TR000448, and R01 EB009352).