Role of N‐Acetylaspartate in Alzheimer Disease

Alzheimer's disease (AD), one of the most common neurodegenerative disorder is well characterised by the accumulation of insoluble amyloid plaque, a highly ordered protein aggregates in the brain. Recently, with the advent of a technique (proton magnetic resonance spectroscopy) for monitoring the changes in the levels of brain metabolites during the disease progression, a decrease in N‐Acetylaspartate (NAA) and an increase in Myoinositol (mI) levels have been most consistently detected in the brains of AD patients. On such grounds, both of them were often regarded as a valuable marker for diagnosis of Alzheimer's disease. A relationship between the formation of protein aggregates and the changes in the level of these two markers has not been studied. We therefore investigate the effect of NAA and mI on aggregation profile of an aggregation model protein, bovine carbonic anhydrase. Aggregation of bovine carbonic anhydrase was monitored by observing the change in the light scattering intensity at 500 nm using a Jasco V‐660 UV visible spectrophotometer equipped with a Peltier‐ type temperature controller. Here, we found that while NAA can completely offset the extent of bovine carbonic anhydrase aggregation, mI has no significance effect on aggregation even at highest concentration. We also found that NAA‐mI mixture has synergistic effect on the aggregation process. This study indicates the importance of NAA level in the brain cells of AD patients to control the deposition of protein aggregates. Source of research support: This work was supported by the grant from the Department of Science and Technology (Ref. no: SR/SO/BB‐0003/2011). Authors acknowledge Council of Scientific and Industrial Research for the financial assistance provided in the form of research fellowship (File. no. 09/045(0992)/2010‐EMR‐1).