[이데일리 이광수 기자] Alzheimer’s disease, a typical intractable brain disease, has not been clearly analyzed so far. In the case of Alzheimer’s, it has been assumed that this is the main cause of the disease by seeing the accumulation of debris (plaque), such as amyloid beta protein or tau protein, on the outside of brain cells.
This is the most widely accepted ‘amyloid beta hypothesis’. Brain cells begin to damage following plaques, such as amyloid, build up outside the brain cells. Treatments currently approved by the U.S. Food and Drug Administration (FDA) are also designed with a mechanism to remove the plaque.
Recently, a research team led by Lee Joo-hyun at New York University published a new study on the cause of Alzheimer’s disease. According to the research results published on the 2nd (local time) as a cover article for the online edition of Neuroscience, a world-renowned academic journal, it was analyzed that the destruction of brain cells that remove wastes occurs earlier than the accumulation of plaques such as amyloid beta.
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Joohyun Lee’s research team at NYU observes cell damage before plaque accumulation
Until now, many scientists have pointed to the accumulation of plaques, such as the protein amyloid beta, on the outside of brain cells as the first step in brain damage. Professor Lee’s research team presented a different perspective from the existing ‘amyloid beta hypothesis’ by revealing that brain cells and nerves are damaged before plaque builds up.
The study traced the root dysfunction observed in mice bred to develop Alzheimer’s disease with brain cell lysosomes. Lysosomes are small organs inside our body cells. In lysosomes, there are protein enzymes that remove waste products generated during the cell’s metabolism.
The researchers found a decrease in acid activity inside the lysosome as a result of Alzheimer’s disease. It was shown that these lysosomes expand as they fuse with vacuoles filled with undigested waste. In particular, in severely damaged neurons, these vacuoles protrude from the cells in a flower-like pattern, and plaque builds up on the outside.
Dr. Joo-Hyeon Lee, who led the study, explained, “Our study results are the first study on the problem inside the brain cell lysosome, where the amyloid beta protein first appears in the nerve damage found in Alzheimer’s disease patients.”
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Expectation of new treatments
“This new evidence changes our fundamental understanding of how Alzheimer’s disease progresses,” said senior researcher Ralph Nixon. “It explains why many of the experimental therapies devised did not stop disease progression.”
“This study suggests that future therapies should focus on reversing lysosomal dysfunction and rebalancing acid levels inside brain neurons,” he said. At the same time, the team said they were already working on treatments to treat the lysosomal problems observed in the study.
The most recent FDA-approved treatment for Alzheimer’s disease is Biogen (BIIB) aduhelm. Aduhelm is a mechanism for reducing amyloid beta protein according to the amyloid beta hypothesis, but its effectiveness has been questioned and has not been commercially successful.
