There have been major advances over the last several years in the molecular genetics of Alzheimer's disease (AD) as well as identification of genes and pathways important in cell death, particularly apoptosis. Utilizing this information, transgenic (TG) and knockout (KO) mice have been developed which can be utilized as powerful tools to study the role of specific genes in AD, to determine whether apoptosis and genes important in programmed cell death contributed to AD, and to better understand the effect of AD-genes important in programmed cell death contribute to AD, and to better understand the effect of AD-related genes on neuropathology and behavior. While there are now excellent TG models to study certain aspects of AD-related neuropathology such as Abeta deposition, clear-cut evidence of selective neuronal death has not yet been observed in these mice. In addition, the effects of a major risk factor for AD, the E4 allele of apolipoprotein (apoE), on both AD neuropathology and behavior is only beginning to be studied. It seems likely that more features of AD neuropathology including neuronal dysfunction, neurotransmitter abnormalities, behavior dysfunction, and susceptibility to cell death can be studied in current and newly developed mouse models. The purpose of this core is to integrate and facilitate the use of TG and KO mice in the Core and specific projects with behavioral and morphometric studies. The purpose of this core is to integrate and facilitate the use of TG and KO mice in the Core and specific projects with behavioral and morphometric studies. An additional goal of this Core will be to serve a consulting role for stereological studies in other projects.
The specific aims are as follows:
Aim 1 : To breed and maintain colonies of molecular characterized TG and KO mice with appropriate controls for utilization by studies in other projects as well as the Core.
Aim 2 : To perform behavioral studies to characterize the neuropsychiatric effects of specific genes and treatment of TG and KO mice produced and maintained in Aim 1.
Aim 3 : To perform histological and neuropathological analysis to characterize extent and type of cell death, degree of AD-like pathology, and the presence of specific fiber and synaptic abnormalities in the mice behaviorally characterized and produced and analyzed in Core B and Project 3. In addition, the Core will serve a stereological consulting role for the other projects.
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