MOUSE MODELS OF LOCAL NGF AND ACETYLCHOLINE DYSFUNCTION

$176,378P01FY2002AGNIH

Salk Institute For Biological Studies, La Jolla CA

Investigators

Linked publications, trials & patents

Paper 29535375 Paper 29045838 Paper 28130011 Paper 28067668 Paper 27558862 Paper 27525439 Paper 27466341 Paper 27419933 Paper 26948893 Paper 26903653 Paper 26620558 Paper 26489892 Paper 26388203 Paper 26341908 Paper 26302439 Paper 26202279 Paper 25803611 Paper 25788688 Paper 25673831 Paper 25533483 Paper 25505106 Paper 25448159 Paper 25173807 Paper 25126588 Paper 25093680 Paper 25024337 Paper 25022790 Paper 24885390 Paper 24825898 Paper 24813892 Paper 24462903 Paper 24068826 Paper 23935974 Paper 23626796 Paper 23413261 Paper 23401561 Paper 23392688 Paper 23384597 Paper 23313024 Paper 23254192 Paper 23223568 Paper 23182244 Paper 23152192 Paper 22989354 Paper 22833673 Paper 22810100 Paper 22647715 Paper 22528101 Paper 22514658 Paper 22508489 Paper 22492998 Paper 22456708 Paper 22314685 Paper 22281106 Paper 22229116 Paper 22211740 Paper 22150925 Paper 22112803 Paper 22066148 Paper 22064070 Paper 21998872 Paper 21994367 Paper 21928509 Paper 21860085 Paper 21403389 Paper 21368891 Paper 21358740 Paper 21304989 Paper 21296890 Paper 21257908 Paper 21103359 Paper 21045796 Paper 20970422 Paper 20679195 Paper 20559548 Paper 20554871 Paper 20445049 Paper 20433905 Paper 20413653 Paper 20181623 Paper 20140000 Paper 20091183 Paper 19944097 Paper 19932737 Paper 19931251 Paper 19864570 Paper 19726646 Patent 7674455 Patent 7328129 Patent 7244423 Patent 7157435 Patent 7101540 Patent 6998118 Patent 6875569 Patent 6815431 Patent 6683058 Patent 6680292 Patent 6451306 Patent 6300488 Patent 5919667

Abstract

Alzheimer's Disease (AD) is characterized by the presence of intraneuronal tangles and extracellular amyloid plaques, which are accompanied by neurodegeneration and cognitive impairment. The major goal of this Program Project is to develop animal models that are useful not only for the understanding of the molecular and neural mechanisms of neuronal degeneration and impaired learning and memory in AD, but which are also amenable to the development of effective strategies for gene therapy of AD. Project 2 focuses on the roles of nerve growth factor (NGF), the neurotrophin receptor p75, and acetylcholine (ACh) within central cholinergic systems in learning and memory. NGF, p75m, and choline acetyltransferase (ChAT)(the biosynthetic enzyme) for ACh), conditional mutant mice established by the Cre-LoxP system will be injected with viral vectors expressing Cre into specific regions of adult brain to remove these molecules. Furthermore, mutations in the gene encoding the amyloid precursor protein (APP) have been discovered in familial AD patients, implicating APP in the etiology of AD. Several lines of in vitro evidence suggest that neurotrophins and p75 might modify the expressing, processing, or functions of APP or the aggregation of its processed products, including beta-amyloid. Conversely, APP and its processed products may influence neurotrophin signaling. NGF and p75 mutant mice will e crossed with transgenic mice expressing mutated human APP that display neuroanatomical alterations resembling AD. Time-course of neuroanatomical alterations and behavioral deficits will be determined in these compound mice. The aims are: Aim 1. To determine the role of p75, nerve growth factor (NGF) and acetylcholine (ACh) in the survival and function of adult basal forebrain cholinergic neurons (BFCNs). Aim 2. To determine the role of p75 and NGF in the neurotoxicity of beta-amyloid in adult BFCNs.

View original record on NIH RePORTER →