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Full-Text Articles in Medicine and Health Sciences

The Role Of Apolipoprotein E In Regulating Tau Pathogenesis And Neurodegeneration In A Tauopathy Mouse Model, Yang Shi Dec 2018

The Role Of Apolipoprotein E In Regulating Tau Pathogenesis And Neurodegeneration In A Tauopathy Mouse Model, Yang Shi

Arts & Sciences Electronic Theses and Dissertations

APOE4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). APOE4 increases brain amyloid-β (Aβ) pathology relative to other APOE isoforms. However, whether APOE independently influences tau pathology, the other pathological hallmark of AD and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human APOE knock in (KI) or APOE knockout (KO) background, we show that the presence of human APOE, regardless of APOE isoforms, leads to various degrees of brain atrophy in 9-month old P301S mice, whereas APOE ablation strongly protects against neurodegeneration. In particular, P301S/E4 mice develop …


Therapeutic Effect Of Rho Kinase Inhibitor Fsd-C10 In A Mouse Model Of Alzheimer's Disease., Qing-Fang Gu, Jie-Zhong Yu, Hao Wu, Yan-Hua Li, Chun-Yun Liu, Ling Feng, Guang-Xian Zhang, Bao-Guo Xiao, Cun-Gen Ma Nov 2018

Therapeutic Effect Of Rho Kinase Inhibitor Fsd-C10 In A Mouse Model Of Alzheimer's Disease., Qing-Fang Gu, Jie-Zhong Yu, Hao Wu, Yan-Hua Li, Chun-Yun Liu, Ling Feng, Guang-Xian Zhang, Bao-Guo Xiao, Cun-Gen Ma

Department of Neurology Faculty Papers

Fasudil, a Rho kinase (ROCK) inhibitor, effectively inhibits disease severity in a mouse model of Alzheimer's disease (AD). However, given its significant limitations, including a relatively narrow safety window and poor oral bioavailability, Fasudil is not suitable for long-term use. Thus, screening for ROCK inhibitor(s) that are more efficient, safer, can be used orally and suitable for long-term use in the treatment of neurodegenerative disorders is required. The main purpose of the present study is to explore whether FSD-C10, a novel ROCK inhibitor, has therapeutic potential in amyloid precursor protein/presenilin-1 transgenic (APP/PS1 Tg) mice, and to determine possible mechanisms of …


The Famous Names Discrimination Task As A Biomarker Of Alzheimer's Disease Risk: An Erp Study, Elizabeth Rose Paitel Apr 2018

The Famous Names Discrimination Task As A Biomarker Of Alzheimer's Disease Risk: An Erp Study, Elizabeth Rose Paitel

Master's Theses (2009 -)

Current ERP research emphasizes age- and pathology-related declines in neural processing in the form of attenuated amplitudes and prolonged latencies. Notably, there is a gap in the ERP literature regarding neural processing trajectories in the time between healthy young adulthood and clinical MCI/AD samples. fMRI research, however, has demonstrated periods of increased, compensatory activation in healthy, cognitively intact APOE ɛ4 carriers both during resting state and event-related tasks (Bondi, Houston, Eyler, & Brown, 2005; Evans et al., 2014; Filippini et al., 2009; Rao et al., 2015), consistent with compensatory theories of cognitive aging (Cabeza, 2002; Park & Reuter-Lorenz, 2009; Reuter-Lorenz …


Representing Diversity In The Dish: Using Patient-Derived In Vitro Models To Recreate The Heterogeneity Of Neurological Disease, Layla T. Ghaffari, Alexander Starr, Andrew T. Nelson, Rita Sattler Feb 2018

Representing Diversity In The Dish: Using Patient-Derived In Vitro Models To Recreate The Heterogeneity Of Neurological Disease, Layla T. Ghaffari, Alexander Starr, Andrew T. Nelson, Rita Sattler

Department of Neuroscience Faculty Papers

Neurological diseases, including dementias such as Alzheimer's disease (AD) and fronto-temporal dementia (FTD) and degenerative motor neuron diseases such as amyotrophic lateral sclerosis (ALS), are responsible for an increasing fraction of worldwide fatalities. Researching these heterogeneous diseases requires models that endogenously express the full array of genetic and epigenetic factors which may influence disease development in both familial and sporadic patients. Here, we discuss the two primary methods of developing patient-derived neurons and glia to model neurodegenerative disease: reprogramming somatic cells into induced pluripotent stem cells (iPSCs), which are differentiated into neurons or glial cells, or directly converting (DC) somatic …


Amyloid-Beta Solubility In The Treatment Of Alzheimer's Disease, Michael Paul Murphy Jan 2018

Amyloid-Beta Solubility In The Treatment Of Alzheimer's Disease, Michael Paul Murphy

Molecular and Cellular Biochemistry Faculty Publications

No abstract provided.


Therapeutic Cocktail Approach For Treatment Of Hyperhomocysteinemia In Alzheimer’S Disease, Michael Leon, Darrell Sawmiller, R. Douglas Shytle, Jun Tan Jan 2018

Therapeutic Cocktail Approach For Treatment Of Hyperhomocysteinemia In Alzheimer’S Disease, Michael Leon, Darrell Sawmiller, R. Douglas Shytle, Jun Tan

Neurosurgery and Brain Repair Faculty Publications

In the United States, Alzheimer's disease (AD) is the most common cause of dementia, accompanied by substantial economic and emotional costs. During 2015, more than 15 million family members who provided care to AD patients had an estimated total cost of 221 billion dollars. Recent studies have shown that elevated total plasma levels of homocysteine (tHcy), a condition known as hyperhomocysteinemia (HHcy), is a risk factor for AD. HHcy is associated with cognitive decline, brain atrophy, and dementia; enhances the vulnerability of neurons to oxidative injury; and damages the blood–brain barrier. Many therapeutic supplements containing vitamin B12 and folate have …