AD Concept- OLFACTION AS AN EARLY BIOMARKER OF AD

在嗅觉的四个功能领域(气味识别、辨别、检测和记忆)中，气味识别似乎比AD患者的其他领域受到的影响更大。这里提出的研究将探索在蠕虫和小鼠模型系统中AD进展的不同阶段中嗅觉功能的参与。这项拟议的研究将：i)研究补充烟酰胺腺嘌呤二核苷酸(NAD)在ApoE AD线虫模型中的作用模式；ii)确定并表征与非AD对照组小鼠相比，AD小鼠嗅球差异表达基因的动力学；以及iii)分析小鼠嗅觉功能障碍与AD病理之间的相关性，作为小鼠年龄和使用或不使用NAD补充治疗的函数。这些研究的结果将使用新的蠕虫和已建立的AD小鼠模型来确定AD相关嗅觉缺陷的性质和动力学，并确定嗅觉功能作为NAD补充治疗效果的读数的潜在用途。

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.