It is well documented that pet cats develop age-related diseases similar to humans with chronic age-related diseases, including Alzheimer’s disease (AD). Since pet cats live in the same environment as their owners and by extension are subjected to the same environmental stressors, older pet cats are an excellent mammalian model to study therapeutic targets to slow or reverse brain aging. However, aging within the brains of pet cats is not well characterized, partly because valid reagents have not been identified. This study was designed to test several human-specific antibody reagents that identify non-neuronal cells, aging pathways, and Aβ amyloid and phosphorylated tau (pTau) seen at autopsy in brains from patients with AD. Archived brain samples, collected from pet cats at autopsy, were graciously provided by the veterinary pathology departments at University of California Davis campus and University of Pennsylvania. Immunohistochemistry staining was done to detect: 1) Microglia, a non-neuronal inflammatory reactive cell type, using an IBA1-specific marker; 2) An inflammatory pathway using an MCP-specific marker; 3) Amyloid plaques using E610, an Aβ42-specific marker; and 4) pTau fibrillary tangles using AT8, a pTau-specific marker. A digital imaging software program was used to generate a heat map to visualize staining and quantify results. It was found that brain samples from older pet cats had increased inflammation as determined by high staining intensity of microglia and MCP1. Brains from several cats showed evidence of amyloid plaques and pTau tangles. These observations suggest that the human-based reagents tested can identify analogous cell types, pathways, and pathogenic components of AD in brains from pet cats. These prototype reagents can now be used to begin the task of characterizing neuropathology in deceased pet cats donated to the Cat Alzheimer’s disease Program at the University of Washington.

Alzheimer's disease (AD) is a neurodegenerative age-related disease characterized by the presence of amyloid-beta aggregates and hyperphosphorylated tau tangles. It has been well documented that cognitive decline and changes in age-related pathways are associated with disease progression. Mitochondria play an important role in degradation of amyloid protein through a mitochondrial protein-mediated quality control system. This pathway can break down with increasing age and lead to the overwhelming presence of amyloid, disrupting normal mitochondrial activity. This damage leads to the formation of more Aβ plaques and neuroinflammation, contributing to the pathogenesis of AD. Mitochondrial regulators may be potential therapeutic drug targets but models are needed to help identify and characterize them. In this regard, an Adeno-Associated-Viral (AAV) vector was used to induce AD protein expression in the brains of old mice. 40 Male and 40 Females mice aged 24 months were infected with either the AAV-AD or AAV-SHAM vector and given 3 months for expression of the proteins to build. Mice were euthanized and brain tissue collected into formalin, with the hippocampus cut into slides for immunohistochemistry (IHC). Data generated from these mice has shown trends in decreased synaptic integrity, increased inflammation and DNA damage associated with expression of the vector proteins. Utilizing the same model, this experiment aims to understand how expression of the AAV-AD proteins may be associated with known roles of mitochondria and characterized pathways in the early stages of AD. IHC was performed using antibodies specific for PITRM1, a mitochondria protein degradation regulator, and PINK1, responsible for mitochondrial-mediated cell death (mitophagy). Imaging software “ImageJ” will be used for quantitative analysis of the stains. This study will help clarify an association between varying levels of AD protein expression and mitochondrial regulation, providing valuable information for enhancing therapies aimed at preventing the progression of early stage AD.

Early-Stage Alzheimer’s Disease (ESAD) is characterized by the development of beta-amyloid aggregates (Aβ42) and phosphorylated tau (pTau) leading to mild cognitive decline and variable personality changes. Because specific diagnostic criteria have not yet been established for ESAD at middle age, there is no way of knowing who might be susceptible and who might be resilient to more severe neuropathology and dementia in later years. The geroscience concept assumes pathways associated with aging are also associated with age-related diseases including ESAD. Therefore, a simple skin biopsy procedure shown to predict resilience to aging in middle-aged mice should be able to predict resilience to ESAD in middle-aged mice. An adeno-associated-viral (AAV) vector system carrying pathogenic components of AD, Aβ42, and pTau, was used to induce ESAD in 23-month-old C57BL/6 mice. Before receiving the AAV vector, 2 mm ear punch biopsies were performed, and the rate of closure was measured over 3 weeks. The study ended when mice were 26 months of age, and the closure rate for each mouse was calculated and correlated with behavioral and neuropathological features of EASD. Preliminary observations will help address the question of whether the healing rate of a simple skin wound can predict susceptibility to the burden of AAV-mediated ESAD. It is expected increases in physical resilience will be associated with increased wound closure, and thus, mice with increased wound closure will have greater resilience to the onset of ESAD neuropathology. This could have highly impactful implications for the early treatment of ESAD in human patients thus preventing the irreversible and fatal progression of dementia associated with late-stage AD. In addition, DNA from skin biopsy cores could be used to obtain DNA methylation signatures for determining biological age thus providing an enriched, translationally relevant data set.
 

The variation in traits associated with fitness often results in selective pressures, thereby influencing the phenotypic traits observed in populations across diverse environments. The exploration of differences among individuals within and between populations has consistently been a key emphasis in evolutionary biology, seeking to understand how organisms adapt to a range of environments. In this research, I analyzed pelage color variation in the least chipmunk (Tamias minimus). Focusing on intraspecific variation—differences observed within a species—I conducted a quantitative analysis of pelage brightness across populations distributed throughout the range of the least chipmunk. This species is well-suited for this study because of its extensive geographic range, encompassing a variety of environments that span from semi-arid shrub steppe to high-elevation forests. I investigated the relationship between chipmunk habitat, utilizing various environmental variables, and pelage brightness. I predicted that precipitation and temperature would influence the brightness of the pelage, which often corresponds to the ability of an individual to camouflage or thermoregulate in their environment. To test this hypothesis, I photographed 334 museum specimens and measured the mean and standard deviation luminosity (two measurements of brightness) along four dorsal stripes and the head. I then extracted environmental variables using the GPS coordinates for each individual, these included 19 bioclimatic variables, elevation, latitude, net primary productivity and other variables related to geographic location. To examine the influence of environmental factors on the pelage color, I conducted generalized least squares analyses and principal component analyses in R. The initial results of my research indicate that the pelage color of a population is influenced the environment. Most notably, there is a significant correlation between pelage color and precipitation. In habitats with increased precipitation, such as forests, chipmunks tend to exhibit darker colors, whereas in regions with low precipitation, like deserts, individuals often display brighter pelage.