Drug-free ultrasound approach shows promise in clearing Alzheimer’s pathology

A Korean research team has discovered a method to remove Alzheimer’s disease–related pathology using ultrasound, without relying on drugs.

Hallym University Dongtan Sacred Heart Hospital announced Tuesday that Professor Kim Jae-ho’s team in the Department of Neurology demonstrated a way to physically break down and clear amyloid plaques, a key causative factor in Alzheimer’s disease, using only the mechanical energy of ultrasound, without pharmaceutical intervention.

From left, Professor Kim Jae-ho, Dr. Kim Hyung-min, and Professor Kim Young-soo (Courtesy of Hallym University Dongtan Sacred Heart Hospital)

The study, titled “Clearance of amyloid plaque via focused ultrasonication,” also involved Dr. Kim Hyung-min of the Korea Institute of Science and Technology (KIST)’s Bionics Research Center and Professor Kim Young-soo from Yonsei University’s College of Pharmacy.

Current Alzheimer’s antibody treatments, such as lecanemab and donanemab, work by having immune proteins bind to amyloid beta (Aβ)—a protein widely regarded as a key driver of Alzheimer’s pathology—thereby triggering immune-mediated clearance.

However, despite their therapeutic effects, these treatments face limitations due to high costs and potential side effects, including brain edema and intracerebral hemorrhage.

Seeking alternatives, the research team explored low-intensity focused ultrasound (LIFU) therapy as a drug-free option. This approach targets specific brain regions by concentrating ultrasonic energy—similar to how a magnifying glass focuses sunlight—to mechanically disrupt aggregated protein structures through vibration.

(Source: Theranostics)

The efficacy of ultrasound treatment was confirmed in both in vitro experiments and animal models. In test-tube experiments, treated amyloid beta showed a 62 percent reduction in rigid fibrillar structures and a 65 percent reduction in toxic oligomers.

In mouse models of Alzheimer’s disease, ultrasound treatment led to a clear reduction in amyloid plaques. Amyloid levels in the bloodstream increased by 66 percent, suggesting that the fragmented proteins were broken down and expelled via circulation, the team said.

The researchers then administered ultrasound-treated amyloid aggregates to human-derived SH-SY5Y neuroblastoma cells to assess changes in toxicity. SH-SY5Y cells closely mimic the biological characteristics of human neurons and are widely used in Alzheimer’s research. The results showed that cell survival rates, which were 82 percent when exposed to untreated amyloid aggregates, increased to 90 percent with ultrasound-processed aggregates, indicating reduced toxicity.

“This study shows that pathological brain proteins can be disrupted and cleared using only the mechanical energy of ultrasound, without drugs or surgical intervention,” Professor Kim Jae-ho said. “This technology may also be applicable to other neurodegenerative diseases, including Parkinson’s disease.”

He added, “We plan to develop patient-tailored ultrasound treatment protocols and aim to create new therapeutic options for Alzheimer’s disease. Our goal is to deliver research outcomes that provide hope for patients and families affected by severe neurological disorders.”

The study was published in the international journal Theranostics and was also featured in ‘People Who Shine for Korea,’ a selection curated by the Biological Research Information Center (BRIC).

The research was supported by the National Research Foundation of Korea, KIST, and the National Research Council of Science and Technology.