Novel Approaches to Alzheimer's Disease

A study has suggested radical new approaches to the diagnosis and treatment of Alzheimer's disease.

The investigators question the current theory that the dementia in Alzheimer's is caused by plaque deposits in the brain. They argue that, instead, the disease may be caused by a fundamental defect in the brain's ability to configure the newly synthesized proteins that are necessary for memory. They offer evidence that the presence of beta-amyloid, the primary component of the plaque deposits, is only a marker of the dementia, rather than the cause. The study, from the laboratory of Jordan L. Holtzman at the University of Minnesota (Minneapolis, USA), was published in the June 24, 2005, issue of Biochemical Biophysical Research Communications.

The investigators outline several flaws in current approaches that link the disease to the toxicity of the beta-amyloid. They note that longitudinal studies of elderly subjects have shown that up to 40% of those with plaque deposits were not demented at the time of death. Similarly, despite the fact that beta-amyloid is produced in everyone, the deposits are only seen in the elderly. This suggests that the beta-amyloid is bound to carrier proteins, which keep it in solution. The study presents data indicting that Alzheimer's may result from a fundamental failure of the nerve cells to produce these carrier proteins.

Determining the levels of the carrier proteins in the cerebrospinal fluid may be a useful test to diagnose and monitor the disease, according to the researchers. Also, new agents should be developed that enhance the ability of cells to produce functional proteins, such as methoxychlor, shown effective in animal studies. In the meantime, drugs that either block the synthesis of the beta-amyloid or dissolve the plaque have been uniformly unsuccessful in moderating the disease.




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