Genetic Interaction Between Lsd1 And Hyperphosphorylated Tau
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Rohitha Moudgal
NBB 495A Fall 2015
Honors Proposal
Investigating a Genetic Interaction Between LSD1 and Hyperphosphorylated Tau in a P301S Mouse Model
Background
Alzheimer’s disease is the most common form of dementia and is characterized by the degeneration and death of brain cells that causes a loss of mental function. Although neuronal loss is not considered a normal part of aging, age is a significant risk factor for Alzheimer’s disease (AD) (Lindsay et al., 2002). Hallmarks of AD include tau tangles and Amyloid-β plaques, whose interaction is thought to lead to neuronal death (Ittner & Götz, 2011). At present, there is no singular cause identified for AD, and further study is required before a cure can be developed. One proposed link to AD is a mutation in Microtubule Associated Protein Tau (MAPT), coded by the MAPT gene located on chromosome 17 (Lee, Goedert, & Trojanowski, 2001). Tau protein is normally soluble and functions to stabilize microtubules within axons. However, mutations in MAPT can cause Neurofibrillary Tangles (NFTs) comprised of hyper-phosphorylated tau protein to collect within neurons and spread throughout the brain (Clavaguera et al., 2009). These tau tangles are detergent-insoluble and impair axonal transport to an extent (Zhang et al., 2012). Transgenic mice expressing mutant human P301S tau protein exhibit synaptic dysfunction followed by hippocampal and cortical neuronal loss (Yoshiyama et al.,