Diagnosing the Prodromal State of Alzheimer's Disease

Mild Cognitive Impairment- Amnestic Subtype (MCIa) is a putative prodromal stage of Alzheimer’s Disease (AD) characterized by focal deficits in episodic verbal memory. Less is known about relative deficits in visuospatial learning, although there is ample evidence indicating involvement of the hippocampus in visuospatial learning, as well as hippocampal degeneration in early AD. The aim of this study was to better characterize the components of working memory dysfunction in people with MCIa to increase the ability to reliably diagnose this disease. Fifty-six elderly adults diagnosed with MCIa and 94 healthy elderly completed a hidden maze learning task. Results indicated similar functioning between groups on measures of reasoning, problem solving, and accuracy. However, MCIa subjects were less efficient at learning the hidden path, making more errors per second on average (Cohen’s d= -.78) and requiring a longer time to complete the maze (Cohen’s d=.77). The learning curve between the first two trials was four times as steep for healthy elderly compared to MCIa (slopes = 4.9 vs. 1.24, respectively), indicating that MCIa subjects exhibited relative difficulty in holding and making effective use of an internal spatial map in order to improve performance. Our results suggest that MCIa patients have focal deficits in visuospatial working memory, with relative preservation of functioning on other more global measures of cognitive functioning. This particular pattern of results may be specific to the amnestic variant of MCI.

Biological Signatures of Vaccine Responses

The set of host- and pathogen-specific molecular features of a disease comprise its “signature”. We hypothesize that biological signatures enables distinctions between vaccinated vs. infected individuals. In our research, using porcine samples, protocols were developed that could also be used to identify biological signatures of human disease. Different classes of molecular features will be tested during this project, including indicators of basic immune capacity, which are being studied at this instance. These indicators of basic immune response such as porcine cytokines and antibodies were validated using Enzyme-linked immunosorbent assay (ELISA). This is an established method that detects antigens by their interaction with a specific antibody coupled to a polystyrene substrate. Serum from naïve and vaccinated pigs was tested for the presence of cytokines. We were able to differentiate the presence of porcine IL-6 in normal porcine serum with or without added porcine IL-6 by ELISA. In addition, four different cytokines were spotted on a grating-coupled surface plasmon resonance imaging system (GCSPRI) chip and antibody specific for IL-8 was run over the chip. Only the presence of IL-8 was detected; therefore, there was no cross-reactivity in this combination of antigens and antibodies. This system uses a multiplexed sensor chip to identify components of a sample run over it. The detection is accomplished by the change in refractive index caused by the interaction between the antibody spotted on the sensor chip and the antigen present in the sample. As the multiplexed GCSPRI is developed, we will need to optimize both sensitivity and specificity, minimizing the potential for cross-reactivity between individual analytes. The next step in this project is to increase the sensitivity of detection of the analytes. Currently, we are using two different antibodies (that recognize a different part of the antigen) to amplify the signal emitted by the interaction of antibody with its cognate antigen. The development of this sensor chip would not only allow to detect FMD virus, but also to differentiate between infected and vaccinated individuals, on location. Furthermore, the diagnosis of other diseases could be done with increased accuracy, and in less time due to the microarray approach.