In an open letter, Dr. Scott’s question about the causality of Alzheimer’s disease (AD) sparked debate among experts. Dr. [Author’s Name] responds, acknowledging several points of agreement but disagreeing on key aspects.
The author emphasizes that targeting a causal mechanism offers the greatest therapeutic benefits for AD. They argue that lowering Aβ42 production and/or clearing amyloid deposits can effectively halt or slow neurodegeneration. However, some critics have argued that Aβ accumulation is not the primary cause of AD.
Dr. [Author’s Name] disputes this notion, suggesting that biochemical events initiate neurodegeneration in AD. They cite evidence from multiple lines of research indicating a gradual progression from elevated Aβ42 to inflammation, neurodegeneration, and tissue atrophy.
The author acknowledges the complexity of the issue but emphasizes that both extracellular accumulation and intracellular processes contribute to Aβ-induced cytotoxicity. Cell biological studies have shown that Aβ is generated in endosomal vesicles and secreted by recycling endosomes, which ultimately leads to abnormal Aβ42 accumulation and neurodegeneration.
The author also addresses concerns about the effectiveness of Aβ-lowering trials. While some results may appear limited, they highlight potential benefits in slowing neurodegeneration and clinical progression. In fact, studies have shown that such approaches can effectively halt or slow disease progression.
Ultimately, Dr. [Author’s Name] agrees that future trials testing drugs to clear amyloid or “traffic jams” in the early stages of AD are necessary. However, they emphasize that existing evidence demonstrates the efficacy of such approaches and their potential for improved outcomes even earlier in the disease process.
Source: https://www.alzforum.org/news/community-news/and-response