Alzheimer's disease (AD) is progressive brain degeneration with key symptoms including cognitive impairment and memory decline. AD is marked by three core pathological features, including a build-up of beta-amyloid plaques, neurofibrillary tangles, and sustained immune response in the brain. Age is the largest known risk factor for AD. Diabetes - can increase the risk of developing AD by up to 4 fold. Diabetes is marked by elevated levels of sugar in the bloodstream for a sustained period, also known as chronic hyperglycemia. Several animal and human studies have shown that when in a sustained state of hyperglycemia, it can initiate inflammation in the brain and increase AD pathology. This experiment investigates the effects of high blood sugar levels by examining the neuroinflammatory pathways in the brain to determine whether the increased AD-like pathology diabetes is a result of a hyperglycemic state itself, or if it’s the result of hyperglycemia-induced neuroinflammation. We used immunohistochemistry to measure immune cells (i.e., microglia and astrocytes) in the hippocampus region in the brain, which is involved in learning and memory and is the first region to be affected by AD. The preliminary study did not yield significant differences in regard to neuroinflammation severity. However, we are looking to increase our sample size moving forward in this project. Given the rapidly increased trajectory of diabetes and AD diagnosis, it is important to understand the mechanistic role by which chronic hyperglycemia influences neuroinflammation and AD, to better ameliorate treatments targeting AD.

Blood-based biomarkers for neurodegenerative illnesses such as Alzheimer's disease (AD) have been extensively researched. AD is a neurodegenerative condition characterized by a variety of pathophysiological distinction such as amyloid β peptide aggregation and a gradual decrease in cognitive function. However, the cerebrovascular pathophysiology relationship of this illness remains unknown. It is postulated that dynamic crosstalk between the brain and systemic responses may be crucial. Due to central nervous system proxy and endothelium permeability, peripheral blood cells (PBC) and their abundance are potential indicators of the blood-brain barrier (BBB) postulate. The pathogenesis of PBCs has been related to a negative influence on neurodegenerative illnesses and several peripheral blood cell link pathways have been investigated, yet none have presented a categorical meta-analysis link to AD via abundance and count effect. In this work, we investigated genomic abundance associations of AD populations to peripheral blood cell counts, whilst suggesting cerebrovascular interplay within the AD brain under synergistically genetic enacting biomarkers. Though employing PBC GWAS with AD genotyping data in polygenic index calculations and regression analyses, we associated nine PBC phenotypes with AD case population. Future blood-biomarker determination may supplement clinical diagnosis for early AD detection

Alzheimer’s disease (AD) is a neurodegenerative disease that is characterized by diminished cognitive functioning that leads to memory loss. This cognitive decline is due to the presence of neuroinflammation, amyloid beta (Aβ) plaques, and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein (pTau). Evaluations of AD brain tissues also demonstrated alterations in γ-aminobutyric acid (GABA) and GABAergic signaling. The GABA receptor B (GABAB), found on microglia cells, is associated with the regulation of the immune response. Our previous studies illustrate a relationship between AD pathologies and variations of GABAB. In an amyloid model, we reported significant decreases in the GABAB receptor. In addition, a novel mouse model developed by our lab, with a knockdown of the GABAB receptor on microglia, crossed with the amyloid model, led to significant increases in Aβ. These findings indicate overlap of pathways involved in amyloid pathology and the GABAB receptor. Further examination into the implications of GABAB with tau pathology is necessary. To assess this, our research will use the well-established Tau P301S mouse to investigate changes in several GABAergic signaling mechanisms compared to the wildtype (WT) mice. The goal of this study is to identify any alterations in GABAB. This analysis will require the use of Western blotting to quantify the protein levels of the GABAB subunits; GABAB1 and GABAB2. The exploration of the role that tau pathology has on the modification of the GABAB receptor is crucial to the understanding of AD.

Alzheimer’s disease (AD) is an age-dependent neurodegenerative disease characterized by the pathological progression of aggregated and accumulated amyloid beta (amyloidosis) and hyperphosphorylated tau (tauopathy) leading to cognitive failure. Specific brain regions including the hippocampus, locus coeruleus, and cerebral cortex that are associated with learning and memory function are most susceptible to AD pathology. Cross sectional and longitudinal studies by Cohen et al 2013 and Berkowitz et al 2018 utilize the transgenic rat model (TgF344AD), which expressed the two mutant genes, amyloid precursor protein (swAPP)and presenilin-1 genes (PS1∆E9) resulted in the full expression of AD pathology plaques, hyperphosphorylated tau and development of neurofibrillary tangles. These studies suggest that the onset of cognitive impairment due to disease occurs at 9 months old. In this present study, using the hippocampus dependent spatial version of the Morris Water maze task, we assessed the precise age-of-onset of cognitive impairment in TgF344AD and wildtype (WT) male and female rats at 4, 5, 6 months and 8,9,10-months-of-age. Current results suggest regardless of sex, there are no significant differences observed in spatial memory performance between the AD and WT rats at 4,5,6-month-old. Ongoing testing of the 8,9,10-month-old rats enables for the determination of the precise age of onset due to AD pathology. Additionally, these rats will also be tested on the elevated zero (EZ) maze task to evaluate neuropsychiatric anxiety-like behavior associated with early development of AD. These results may procure a deeper understanding of the early cognitive and behavioral characteristics of AD progression.