Therapeutic Effects of Itraconazole Analog PRR851 in h-Tau Mice Modeling Alzheimer’s Disease

Alzheimer’s disease is an age-related, neurodegenerative disease characterized by cognitive decline, memory loss, cell death, as well as difficulties in thinking, reasoning, and decision-making skills. It is the world’s most common form of dementia, and it is estimated that roughly six-million American’s currently suffer from Alzheimer’s disease (National Institute for Health, 2021). These deficits are a result of abnormal levels of phosphorylated tau proteins, eventually clumping together to create tau tangles, as well as amyloid- β (Aβ) plaques. Phosphorylated tau interferes with the intracellular transport of material within cells and increases the rate of disease progression. Aging leads to changes that are not only physical, but psychological, behavioral, and physiological as well. It is the inability for the brain to adapt which is seen to be exaggerated in Alzheimer’s disease. Aging can be a leading risk factor in the onset and progression of not only Alzheimer’s disease, but several other chronic diseases. In Alzheimer's disease, the brain’s impairment is primarily due to the presence of the tau protein. In recent findings, a novel compound, PRR851, has been used to block the entry of extracellular vesicle-carried tau into the nucleus of recipient cells. In the current study, we hypothesize that this compound, PRR851, will have therapeutic effects on the pathogenesis of Alzheimer’s disease within a mouse model containing human tau. Thus, we hypothesize that the experimental tau/drug group will statistically perform better than both the tau/saline and wildtype/saline control groups during behavioral assessment. Results from this study did not support our hypotheses. Results showed that wildtype mice performed better than tau mice. These results were consistent with expected h-Tau mice behavior and wildtype/saline behavior. There were no significant differences between the tau/drug group and tau/saline group, indicating that the drug did not enhance performance as we hoped it would. But this may be due to the fact that the first batch of the drug was contaminated during transit.