Aβ-淀粉样蛋白代谢通路基因相关神经网络动态演变模式在阿尔茨海默病风险人群早期诊断中的作用

Impaired memory function for the core clinical features of amnestic mild cognitive impairment (aMCI) and mood disorders as the main manifestation of late-life depression (LLD), who are associated with high risk of Alzheimer's disease (AD). Little is known about the dynamic neural networks model based on genetic imaging strategy of β-amyloid (Aβ) protein metabolic pathway in the AD risk populations. In the present study, we recruited the aMCI patients, LLD patients and well matched controls with age, gender and education. Full-scale neuropsychological tests were used to evaluate the cognitive function in these subjects, and three-year longitudinal multi-modality fMRI was then performed. The present study yielded four main research directions: (1) To reveal the relationship between genetic factors and cognitive key brain regions and whole brain network. (2) To explore the intrinsic association and differences of AD risk populations in the neuroimaging characteristics of dynamic neural networks model based on Aβ protein metabolic pathway. (3) To assess the diagnostic value of the AD-risk populations using the clustering effect of the gene polymorphisms of Aβ protein metabolic pathway. (4) To provide a theoretical basis for preventing or delaying the the progression of aMCI and LLD patients and for the early diagnosis and treatment of AD.

记忆功能受损为核心临床特征的遗忘型轻度认知障碍（aMCI）及情绪障碍为主要表现的老年期抑郁（LLD）患者均是阿尔茨海默病（AD）的高风险人群。基于Aβ-淀粉样蛋白代谢通路相关基因的随访遗传影像学策略探寻AD风险人群的神经环路动态演变模式在国内外尚处于空白。研究团队将在中国汉族人群中同期选择aMCI和LLD患者及其匹配健康对照组人群进行三年随访研究，结合多模态fMRI技术和多维度认知神经心理量表测试，从Aβ-淀粉样蛋白代谢通路水平上随访探讨不同AD风险人群的神经影像特征动态演变的内在关联及相互差异，评估该通路基因多态性的集聚效应对AD风险人群的诊断价值，为预防或延缓aMCI和LLD患者向AD的转化以及AD 的早期诊断与治疗提供理论依据。

记忆功能受损为核心临床特征的遗忘型轻度认知障碍（aMCI）及情绪障碍为主要表现的老年期抑郁（LLD）患者均是阿尔茨海默病（AD）的高风险人群。基于遗传通路相关基因的随访遗传影像学策略探寻AD风险人群的神经环路动态演变模式在国内外尚处于空白。研究团队将在中国汉族人群中同期选择aMCI和LLD患者及其匹配健康对照组人群进行三年随访研究，结合多模态fMRI技术和多维度认知神经心理量表测试，从通路水平上随访探讨不同AD风险人群的神经影像特征动态演变的内在关联及相互差异。本项目研究成果：① 在国际上首次利用基于tau蛋白代谢基因通路、胆固醇代谢通路、胰岛素抵抗通路等多基因水平的遗传影像学策略，探讨了AD高危人群的神经影像损害模式。② 进一步深入探究关键基因（如CLU、APOE）及核心网络（情节记忆网络、默认网络）在AD风险人群早期诊断与判断预后中的作用。③ 首次系统性分析AD和老年期抑郁共病机制的遗传学基础，并阐述小胶质细胞Toll样受体基因多态性参与AD发生以及AD神经炎症假说与其疾病发生的关联机制。申请人在该项目资助下，已正式发表或已接收第一作者及通讯作者SCI收录论文11篇（累计IF约47分，其中单篇IF > 5分，计4篇：Brain Structure & Function, IF=5.811；Brain Behavior and Immunity2篇, IF=5.874；Oncotarget, IF=5.008）。正是由于该项目较为突出的工作积累，申请人进一步申请并获得主持国家级和省部级科研项目以及相关奖项。将来的研究拟进一步利用遗传成像策略探讨AD风险人群的神经网络模型，最终为预防或延缓aMCI和LLD患者的疾病进展和AD.早期诊断和治疗提供依据。