Fundamental research about the ketone body therapy for Alzheimer's disearse.

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We have created the Amyloid beta protein toxicity model using rat primary hippocampal culture. Hippocampal cells are taken from 18 day fetal SD rats, which were cultured with absolute serum free medium. We have succeeded low density culture more that 7 days, with well neurites grouth and without increasing glial cells. Exposure of 5μ amyloicl s 1-42 peptide (Aβl-42) decreased cell number and neurite number and length in comparison to control. Addition of ketones to cells exposed to Aβ1-42 doubled the survived cell number and increased cell size and neurite outgrowth compared with cells exposed to Aβ1-42. Even we have developed the septum culture as well as hippocampal culture, the immunostaining with cholinergic neurons is unstable to have a quantitative data at this point.It is known that Aβ1-42 is increased up to 6 fold in brains from patients with Alzheimer's disease and that Aβ1-42 inactivates the pyruvate dehydrogenase (PDH) complex in septal neurons by activating the protein kinase. D-(-)-β-hydroxybutyrate (DBHB) is a normal substrate in brain, with provides Acetyl CoA to TCA cycle directly with bypassing PDH complex, and also produce the reducing agent NADH.It was thought that DBHB could rescue hippocampal neurons from the toxicity of Aβ1-42 with mechanism mentioned above. These data, which resulted that ketone bodies provide a neuroprotective effect against with increased levels of Aβ1-42, suggest that ketone body could be a potential candidate for use in the treatment of Alzheimer's disease and other neurological diseases associated with energy crisis.