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Adriana Saba, MD

Job Title

Research Scientist

Academic Rank

Staff/Research Assistant




Lei Liu, Adriana Saba

Principal Investigator

Lei Liu



Unveiling Extensive Cerebral Amyloid Angiopathy in the Brains of Down Syndrome Dementia Patients Using Leqembi

Scientific Abstract

Leqembi, a humanized monoclonal antibody targeting amyloid β, has secured FDA approval as a treatment for early Alzheimer’s disease (AD), marking a pivotal moment in AD therapy development. Notably, there is growing interest in its potential use for Down syndrome (DS) dementia treatment, given that over 90% of DS patients eventually develop AD.

However, using Leqembi in immunotherapy comes with a critical consideration -Cerebral Amyloid Angiopathy (CAA)-related hemorrhage. CAA involves the buildup of amyloid proteins within the brain and organ blood vessel walls. DS patients have a notably higher CAA prevalence compared to the general population, heightening this risk of severe side effects during Leqembi treatment.

To address this pressing clinical concern, our study aimed to determine if Leqembi can detect CAA structures in post-mortem brain tissues from DS dementia patients. Since Leqembi is a human antibody, conducting immuno-histochemical staining on human tissue without significant background staining presented a technical challenge.

Through a novel method, we successfully demonstrated that Leqembi distinctly labels extensive CAA structures in all seven DS dementia brains examined. This discovery raises heightened concerns regarding the safety and suitability of Leqembi’s use in DS patients, underscoring the need for meticulous evaluation in clinical applications.

Lay Abstract

Leqembi, a special medication, has been approved by the FDA to help treat people with early Alzheimer’s disease. This is a big step in finding better ways to treat Alzheimer’s. Now, researchers are also looking into whether Leqembi can help people with Down syndrome who have memory problems because many of them eventually get Alzheimer’s disease.

But there’s a challenge when using Leqembi. It’s related to a condition called Cerebral Amyloid Angiopathy (CAA), where certain proteins build up in the walls of blood vessels in the brain. People with Down syndrome are more likely to have this problem.

When trying to use Leqembi in people with CAA, there’s a risk of bleeding in the brain. To understand this risk better, we studied brain tissues from people with Down syndrome who had passed away. We used a special method to see if Leqembi could find the CAA in their brains. What we found was that Leqembi could see the CAA in the brains of all the people they studied. This raises important questions about whether Leqembi is safe for people with Down syndrome, and more research is needed to find it out.

Clinical Implications

This study highlights the need for a cautious usage of Leqembi in DS dementia patients. While Leqembi may hold promise in some cases, the heightened risk of CAA-related hemorrhage underscores the importance of thorough evaluation, patient selection, and ongoing monitoring.