AD Concept- OLFACTION AS AN EARLY BIOMARKER OF AD

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Of the four functional domains of olfaction (odor identification, discrimination, detection, and memory), odor identification appears to be more strongly affected than the other domains in AD patients. The studies proposed here will explore the involvement of olfactory functions at various stages of AD progression in worm and mouse model systems. The proposed research will: I) investigate the mode of action of nicotinamide adenine dinucleotide (NAD) supplementation in ApoE AD Caenorhabditis elegans models; II) identify and characterize kinetics of genes differentially expressed in the olfactory bulbs of AD mice relative to non-AD control mice; and III) analyze the correlation between olfactory dysfunction and AD pathology in mice as a function of mouse age and treatment with or without NAD supplementation. The results of these studies will define the nature and kinetics of AD-associated olfactory deficits using novel worm and established mouse models of AD and determine the potential use of olfactory function as a readout for NAD supplementation therapeutic efficacy.