Brain cell death in Alzheimer's disease linked to protein accumulation and insulin biochemistry

21 June 2004

Alzheimer's disease patients often have seemingly unrelated abnormalities in their brain cells. In the current issue of the Journal of Alzheimer's Disease, researchers from the Departments of Medicine and Pathology, Rhode Island Hospital and Brown Medical School, have found, for the first time, a link between several of these abnormalities. Alzheimer-associated neuronal thread protein, AD7c-NTP, can accumulate in the brain and cause the death of brain cells. However, the mechanisms by which AD7c-NTP promotes neuronal death are not known.

In general, changes in intracellular signaling can inhibit survival mechanisms or activate normal cell-death processes. A number of growth factors, such as insulin, insulin-like growth factor, type 1 (IGF-1), nerve growth factor (NGF), and platelet-derived growth factor (PDGF) play a role in keeping neurons alive. By using cell cultures in which AD7c-NTP is overproduced and treating these cells with different growth factors, the authors found that AD7c-NTP interferes with the survival mechanisms mediated by insulin or insulin-like growth factor-1 (IGF-1).

Writing in the article, Suzanne M. de la Monte, M.D., M.P.H., states, "Altogether, the results suggest that AD7c-NTP over-expression produces a state of relative insulin resistance in that insulin-stimulated survival and neuritic growth mechanisms are impaired. From the standpoint of therapeutic intervention, it may prove beneficial to restore insulin signaling mechanisms in neuronal cells that over-express AD7c-NTP by treatment with insulin sensitizer drugs."

The article is "Alzheimer-Associated Neuronal Thread Protein Mediated Cell Death is Linked to Impaired Insulin Signaling" by Suzanne M. de la Monte, M.D., M.P.H. and Jack R. Wands, M.D. It appears in the Journal of Alzheimer's Disease, Vol. 6, Number 3 published by IOS Press.

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