Life Sciences Commons^™

Chemokine Receptor Ccbp2-V41a And Its Role In Inflammation And Alzheimer’S Disease, Allen Weinert, Scott Weber

Journal of Undergraduate Research

The leading cause of dementia in elderly patients is Alzheimer’s disease (AD), a degenerating and fatal neurodegenerative condition. AD is a proteopathic disease caused by extensive accumulation of amyloid beta plaques and neurofibrillary tangles. A recent genomewide association study analyzing 59 AD-associated cerebrospinal fluid (CSF) samples statistically associated chemokine receptor mutant CCBP2-V41A with increased CSF protein levels of the proinflammatory chemokine CCL2. CCBP2 is a known binding partner of CCL2. We hypothesized that CCBP2-V41A receptor alters CSF levels of CCL2 and that raised CCL2 levels alters immune cell function, resulting in amyloid beta deposition in the brain (Figure 1).

Characterization Of Mutant Chemokine (C-C) Motif Receptor-Like 2 (Ccrl2) And Its Role In Inflammation And Alzheimer’S Disease, Meganne Ferrel, Dr. John S. K. Kauwe

Journal of Undergraduate Research

Alzheimer’s Disease (AD) is identified as a proteopathic disease that results from an extensive accumulation of amyloid plaques and neurofibrillary tangles in the brain. Several researchers have discovered that cerebrospinal fluid (CSF) contains biomarkers for AD such as Amyloid-beta and tau. Neuritic plaques in AD are surrounded by activated microglia and astrocytes which can initiate complement and inflammation in the presence of amyloid-beta. Macrophage inflammatory protein chemokine (C-C motif) ligand 4 (CCL4) is a biomarker found in CSF. A high level of expression is associated with risk of developing AD. CCL4 is expressed in a subpopulation of reactive astrocytes and …

Cell Free Single Stranded Dna Concentration In Csf As Biomarker To Diagnose Alzheimer’S Disease, Taylor Avei, Dr. John Kauwe

Journal of Undergraduate Research

The neuropathology of Alzheimer’s Disease (AD) is well-known as a degradation of neural connections in the brain caused by multiple deposits of Amyloid-beta peptide plaques as well as neurofibrillary tangles of tau proteins [1]. Because of this and successful research, both Amyloid-beta 42 and tau protein levels in cerebrospinal fluid currently serve as important biomarkers for the diagnosis of AD according to the New Research Criteria for the Diagnosis of AD provided by the International Working Group (IWG) [2].

Rab10: The Future Of Alzheimer’S Disease, Keni Reid, Dr. John Kauwe

Journal of Undergraduate Research

Alzheimer’s disease is a brain disorder caused by an irreversible degeneration of nerve cells. It is developed in response to a growth of proteins, tau tangles or amyloid plaques, which disrupt communication between neurons in the brain. Because the nerve cells no longer function, they die. It is estimated that as many as 5.1 million Americans may have Alzheimer’s disease and about one to four family members act as caregivers for each individual with Alzheimer’s disease. Many lives are affected by Alzheimer’s which has driven further and extensive research for solutions. However, despite much effort, the genetics of Alzheimer’s remains …

Pvaast Anallysis Of Alzheimer’S Disease Sequencing Project Pedigree Data, Kristen Crofts, John S. K. Kauwe

Journal of Undergraduate Research

Alzheimer’s disease is a progressive brain disorder affecting more than 10 percent of Americans over the age of 65 (1). This disease destroys memory and thinking skills and is a leading cause of dementia. Although research in recent years has provided substantial information related to risk factors associated with Alzheimer’s disease, a great deal of information still remains unknown. PVAAST is a software tool that can analyze genome sequence data of Alzheimer’s patients in a creative way by also analyzing the patients’ pedigree information. With the combined information from family members, it is more feasible to identify genetic mutations related …

Alzheimer’S Risk Genes And Pathways Of Expression, Samantha Jensen, John Kauwe

Journal of Undergraduate Research

Although Alzheimer’s disease (AD) has been the subject of research for nearly 100 years, these decades of research have not led to a unified understanding of the mechanisms behind the disease pathology1 ,2. Recent improvements in whole genome sequencing have made it possible for researchers to find a large number of mutations implicated in AD. Due to a high frequency of false positives and confounding factors, many mutations being investigated for therapies may not even have a causative effect on Alzheimer’s expression. Without concrete knowledge of the interactions of the proteins and genes implicated in the disease, drug development has …

Association Of Tm2d3 Gene With Lateonset Of Alzheimer’S Disease In Cache County, Eleni Tukuafu, Dr. John S. K. Kauwe

Journal of Undergraduate Research

It is estimated that 5.2 million Americans have Alzheimer’s disease. It is currently the 6th leading cause of death in America, killing around 500,000 seniors every year. A 68% increase of death from Alzheimer’s disease was observed from the year 2000 to 2010. These numbers are expected to continue climbing.

Alzheimer’S Disease And The P.V236e Variant In The Apoe Gene, Alton Chad Sorensen, John Kauwe

Journal of Undergraduate Research

I was interested in trying to validate the findings of the publication by Medway et al. concerning the SNP rs199768005 using data from the Cache Country data set. Unfortunately, of the 4703 people from our data set, only 10 were carriers. Using R statistical analysis, I found that the p-value for this SNP with an association to protect for Alzheimer’s Disease (AD) was not significant. It was similarly not significant in its association with Any AD. I also ran other models to include for factors such as education or age in conjunction with this SNP and its association with AD …

Discovery And Confirmation Of Novel Serum Biomarkers Diagnosing Alzheimer’S Disease, Tyler Mower, Dr. John Kauwe

Journal of Undergraduate Research

Background: Alzheimer’s disease (AD) remains challenging to diagnose, especially early disease. Useful serum AD biomarkers would be of great utility in clinical settings and in drug development efforts. We used a novel serum proteomic approach to interrogate the lowmolecular- weight proteome for AD biomarkers.

Experimental design: A discovery study used sera from 58 any-stage AD cases and 55 controls analyzed by capillary liquid chromatography-tandem mass spectrometry. Promising biomarkers were retested in a second, blinded confirmatory study (AD cases=68, controls=57). Several biomarkers replicated and multi-marker sets were modeled.

Results: The initial study found 59 potential AD biomarkers. Thirteen recurred in more …

Importance Of Rare Genetic Variants In Alzheimer’S Disease (Ttc3), Devan Bursey, Dr. John S. K. Kauwe

Journal of Undergraduate Research

Alzheimer’s is a neurodegenerative disease caused by the formation of amyloid plaques and neurofibrillary tangles. Most current research on Alzheimer’s disease has focused on using genome-wide association studies to identify common genetic variants however; past research has shown that rare genetic variants play an important role in the development of Alzheimer’s disease. For example, studies have shown that rare genetic variants in APP, PSEN1, and PSEN2 drastically increase an individual’s risk for Alzheimer’s disease (Tanzi). My research focused on specific rare genetic variant in the TTC3 gene (S1966X). This rare variant has a point mutation that causes a premature stop …

Rare Genetic Variant To The Protection Of Alzheimer’S Disease, Josue David Gonzalez Murcia, John Kauwe

Journal of Undergraduate Research

Alzheimer’s disease is one of the top 10 causes of death in the world and the 6th leading cause of death in the United States, with 5.5 million people diagnosed with the disease. Alzheimer’s cannot be cured, prevented or slowed. Most research with Alzheimer’s disease has been done on SNPs that have a relatively high frequency in the population this has helped facilitate researchers in finding a broad genetic pathway in the development of Alzheimer’s disease (Naj et al. 2011; Harold et al. 2009). Our research will focus on a very rare SNP, with a much lower frequency than previously …

Byu Undergraduates Execute A Familial Study Of Non-Demented Individuals In High-Risk Alzheimer’S Disease Pedigrees, John S.K. Kauwe

Journal of Undergraduate Research

Successful enrollment in and completion of graduate programs requires a constellation of skills. Students must be prepared to plan and execute experiments, present their findings both verbally and in manuscript form and interact effectively with senior scientists in the field of their choice. In this MEG I will mentor four undergraduate students (Kevin Boehme, Lyndsay Staley, Kaitlin Bell and Mark Wadsworth) as they develop skills in study design, data analysis, manuscript preparation, presentation and networking while identifying genetic factors that protect individuals from Alzheimer’s disease.

Rab Proteins And Alzheimer's: A Current Review Of Their Involvement In Amyloid Beta Generation With Focus On Rab10 Expression In N2a-695 Cells, Ivan Arano Rodriguez

Theses and Dissertations

This thesis work describes the role of Rab proteins in amyloid processing and clearance in different cell pathways. It also describes an experimental approach used to analyze the expression effects of Rab10 in amyloid beta production. Since the main theory behind neurodegeneration in Alzheimer's disease claims that high levels of amyloid beta 42 (Aβ42) molecules trigger widespread neuronal death, control of Aβ42 has been a main target in Alzheimer's disease research. In addition, several studies show increased levels of particular Rab proteins in Alzheimer's pathogenesis. However, no review consolidates current findings in neurodegeneration of Alzheimer's with Rab protein dysfunction. The …

Role Of Epistasis In Alzheimer's Disease Genetics, Mark T. Ebbert

Theses and Dissertations

Alzheimer's disease is a complex neurodegenerative disease whose basic etiology and genetic structure remains elusive, despite decades of intensive investigation. To date, the significant genetic markers identified have no obvious functional effects, and are unlikely to play a role in Alzheimer's disease etiology, themselves. These markers are likely linked to other genetic variations, rare or common. Regardless of what causal mutations are found, research has demonstrated that no single gene determines Alzheimer's disease development and progression. It is clear that Alzheimer's disease development and progression are based on a set of interactions between genes and environmental variables. This dissertation focuses …

Mitochondrial Genetics Of Alzheimer's Disease And Aging, Perry Gene Ridge

Theses and Dissertations

Mitochondria are essential cellular organelles and the location of the electron transport chain, the site of the majority of energy production in the cell. Mitochondria contain their own circular genome approximately 16,000 base pairs in length. The mitochondrial genome (mtDNA) encodes 11 protein-coding genes essential for the electron transport chain, 22 tRNA genes, and two rRNA genes. Mitochondrial malfunction occurs in many diseases, and changes in the mitochondrial genome lead to numerous disorders. Multiple mitochondrial haplotypes and sequence features are associated with Alzheimer's disease. In this dissertation we utilized TreeScanning, an evolutionary-based haplotype approach to identify haplotypes and sequence variation …