Grant: Project Grant

Alzheimer's disease (AD) is a brain disease characterized by a gradual loss of memory, followed by deterioration of other cognitive functions such as language, calculation and judgment. The pathological features associated with AD brains include the loss of nerve cells in selected regions along with abnormal deposits of certain molecules such as amyloid-beta (Ab) peptide and tau protein in structures called as plaques and tangles, respectively. The plaques are usually surrounded by activated immune-related cells called astrocytes and microglia. There is evidence that increase levels of Ab peptides may initiate the loss of nerve cells and subsequent development of AD pathology. Although Ab peptides are generated mostly in nerve cells of the brain, it is reported that activated astrocytes located around the plaques accumulate high levels of Ab. Since astrocytes under normal conditions do not generate Ab peptides, it is of clinical relevance to determine the origin of Ab in activated astrocytes and its role in the development and propagation of AD pathology. In a series of experiments, we will establish whether activation of astrocytes can lead to increased production and/or decreased removal of Ab which can subsequently influence loss of neurons. Additionally, we will establish whether activation of astrocytes by Ab peptide can enhance the secretion of small vesicles called exosomes containing Ab peptides which can influence the development/ propagation of AD pathology. Results from this study will highlight the origin and significance of Ab peptides in activated astrocytes and their role in the development/propagation of AD pathology.