An Acute Inflammatory Response in a Diabetic Alzheimer’s Disease Model

Alzheimer’s disease (AD) is the most common form of dementia, accounting for 50 to 80 percent of all dementia cases. This neurodegenerative disease leads to neuronal death and tissue loss in the brain, resulting in the slow deterioration of memory, thinking skills, and eventually even the ability perform daily tasks. While it is not a normal part of aging, AD is mostly diagnosed in people over the age of 65; thus, the main risk factor for Alzheimer’s disease is increased age, though it is most likely other additional factors also contribute (Heese & Akatsu, 2006). Neuropathological hallmarks of AD include neurofibrillary tangles (NFTs) formed by the aggregation of hyperphosphorylated tau proteins, and amyloid plaques formed by the accumulation of β-amyloid (Aβ) proteins (Cvetkovic-Dozic et al., 2001). To date, the etiology of AD remains unknown but several models investigating multiple pathways have been used to better understand the disease. In this experiment, two specific AD risk factors, Type 2 diabetes mellitus (DM) and inflammation of the brain, are of interest. Recent evidence has indicated a connection between Alzheimer’s disease and Type 2 DM. The use of the DM model to investigate AD represents a useful tool to examine AD pathologies. In Type 2 DM, cells fail to use insulin properly, resulting in insulin resistance. This resistance consequently affects the metabolism of tau and Aβ proteins, potentially leading to formation or acceleration of NFTs and amyloid plaques characteristically seen in AD (Gasparini et al., 2002). Chronic brain inflammation, commonly referred to as neuroinflammation, induces a neurotoxic effect by increasing Aβ proteins, senile plaques, and neuronal damage, leading to exacerbated symptoms and a more rapid disease progression. Alternatively, acute inflammatory responses have been suggested to serve a protective role in degenerative disorders (Frank-Cannon et al., 2009). A critical question in AD research is what aspects of chronic neuroinflammation exacerbate pathological features, as well as if an acute inflammatory response may play a neuroprotective role by reducing the aggregation of Aβ, and thus lowering the likelihood of cell loss. The purpose of this study was to investigate the role that acute brain inflammation plays in a diabetic model of AD. In order to examine this, we investigated if an acute immune response induced by lipopolysaccharide (LPS) would alter AD related behavioral or pathological features using the streptozotocin (STZ) diabetic model of AD

McNair Research Journal - Summer 2015

Journal articles based on research conducted by undergraduate students in the McNair Scholars Program Table of Contents Biography of Dr. Ronald E. McNair Statements: Dr. Neal J. Smatresk, UNLV President Dr. Juanita P. Fain, Vice President of Student Affairs Dr. William W. Sullivan, Associate Vice President for Retention and Outreach Mr. Keith Rogers, Deputy Executive Director of the Center for Academic Enrichment and Outreach McNair Scholars Institute Staf