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A core pathological feature of AD is the over-production of reactive oxygen species (ROS), which mediate oxidative stress in the brain. Peroxisomes play a crucial role in mitigating ROS accumulation due to the presence of catalase, an antioxidant enzyme found within the organelle. As the brain ages, progressive dysfunction of peroxisomes and decreased localization of catalase into the organelle contributes to elevated ROS. A suitable therapy to address the increased accumulation of ROS in AD has yet to be identified. Our team has engineered a recombinant derivative of the antioxidant enzyme catalase (CAT-SKL) that specifically targets peroxisomes, thereby providing powerful organelle-based antioxidant and anti-inflammatory effects. In the present study, we aimed to (i) establish the packaging CAT-SKL into macrophage-derived exosomes — endogenous membrane vesicles for the transport of proteins between cells—to effectively target our therapeutic to cells undergoing oxidative stress while minimizing degradation in the bloodstream, (ii) determine the safety and biodistribution in vivo, and (iii) assess the protective effects of prophylactic intranasal administration of exosomes loaded with CAT-SKL (exoCAT-SKL). CAT-SKL was packaged into macrophage-derived exosomes via sonication, and loaded exosomes were purified using size exclusion chromatography or ultracentrifugation. Male and female, control, and 3xTG AD transgenic mice were intranasally administered exoCAT-SKL, and tissues of interest were investigated. The diffuse labelling of CAT- SKL in these mice's brains supports the intranasal administration of exosomes as an effective delivery method to bypass issues surrounding bioavailability, antigenicity, and the blood-brain barrier. Histopathological assessments of the brain and off-target tissue demonstrated no toxicity. Further behavioural and immunohistochemical analysis is required to determine whether exoCAT- SKL can prevent and ameliorate pathological and behavioural outcomes in 3xTG AD mice.

The type, shape, and gradation of aggregate have significant influence upon surface texture and its durability. The properties of reclaimed asphalt pavement (RAP) are different from virgin aggregate. Previous research found that the presence of RAP influenced negatively the pavement surface terminal friction value and surface polishing rate. The objective of this research is to assess the impact of high content of RAP on pavement surface texture after five years of environmental and traffic loading. Field pavement textures were measured on sections with various percentages of RAP. The sections have been in service for five years at the time of testing. The three-dimensional (3D) surface texture is recovered by using a portable line-laser scanning device which has the ability to scan an area of 100 mm x 100 mm of pavement surface with a horizontal resolution finer than 0.05 mm, and vertical accuracy better than 0.1 mm. The recovered 3D texture heights are decomposed into five levels by using discrete wavelet transform to separate macro-texture from micro-texture. 3D texture indices were calculated and analyzed. These 3D texture parameters are indices of texture size both at macro-level and micro-level, spacing, distribution, and texture direction. Texture analysis showed that the macro-texture indices were better for sections with high RAP content than those with low RAP content at the time of testing, while micro-texture parameter shows equal or slightly higher value compared to control mixture. It was also found that the texture durability was slightly worse for high RAP content (50%) sections than those of lower RAP content sections. Pavement core samples were collected and characterized through creep compliance, indirect tensile test and resilient modulus. Laboratory results showed that as the amounts of RAP increases the rutting resistance increases, however, the resistance to low temperature cracking decreases as expected. Presented during Session 24: Topics in PM, moderated by Cesar Queiroz, at the 9th International Conference on Managing Pavement Assets (ICMPA9) in Alexandria, VA. Includes conference paper and PowerPoint slides.