Characterizing the Induction of Senescence by Tau and Beta-amyloid in Rat Astrocytes

Abstract

Alzheimer's Disease characterized by cognitive deficits, memory loss and changes in behavior has no cure currently. Beta amyloid and tau are two main proteins that play a significant role in AD. A mutated Amyloid Precursor Protein abnormally cleaved by beta and gamma secretases causes the accumulation of beta amyloid that lead to the characteristic beta amyloid plaques found extracellularly in AD patients. Tau induces its own adverse effects by hyperphosphorylation and forming neurofibrillary tangles. Aging is the primary risk factor for Alzheimer's Disease (AD). Senescence is a hallmark of aging that can a contributing factors in pathology of AD. there are many overlapping consequences of senescence in AD such as oxidative stress, inflammation and DNA damage. Previous results from our lab have shown that there is an increase in the population of senescent astrocytes in AD patients and beta amyloid as the inducer of the program of senescence. Astrocytes have a vital role in regulating homeostasis at the blood brain barrier and hold a strategic position between the neurons and the capillaries. Astrocyte senescence is considered in this thesis as a contributing factor to AD. Tau, the other hallmark of AD may be also play a role in the induction of senescence in astrocytes. In this thesis, we analyzed the roles of tau and beta amyloid in the activation of senescence in rat by the expression SA-beta galactosidase and mitochondrial membrane potential. Our findings support that tau and beta amyloid have different targets that induce senescence in the astrocytes. The combination of beta amyloid and tau as well as beta amyloid by itself, were well characterized by the expression of SA-beta galactosidase and Tau is shown to be implicated in mitochondrial dysfunction.M.S., Biomedical Engineering -- Drexel University, 201