PDF(Pubmed)
Abstract：
Risk factors of late-onset Alzheimer\'s disease (AD) such as aging, type 2 diabetes, obesity, heart failure, and traumatic brain injury can facilitate the appearance of cognitive decline and dementia by triggering cerebrovascular pathology and neuroinflammation. White matter (WM) microstructure and function are especially vulnerable to these conditions. Microstructural WM changes, assessed with diffusion weighted magnetic resonance imaging, can already be detected at preclinical stages of AD, and in the presence of the aforementioned risk factors. Particularly, the limbic system and cortico-cortical association WM tracts, which myelinate late during brain development, degenerate at the earliest stages. The fornix, a C-shaped WM tract that originates from the hippocampus, is one of the limbic tracts that shows early microstructural changes. Fornix integrity is necessary for ensuring an intact executive function and memory performance. Thus, a better understanding of the mechanisms that cause fornix degeneration is critical in the development of therapeutic strategies aiming to prevent cognitive decline in populations at risk. In this literature review, i) we deepen the idea that partial loss of forniceal integrity is an early event in AD, ii) we describe the role that common risk factors of AD can play in the degeneration of the fornix, and iii) we discuss some potential cellular and physiological mechanisms of WM degeneration in the scenario of cerebrovascular disease and inflammation.
摘要：
晚发性阿尔茨海默病（AD）的危险因素，如衰老，2型糖尿病,肥胖，心力衰竭,创伤性脑损伤可通过引发脑血管病理和神经炎症促进认知衰退和痴呆的出现。白质（WM）的微观结构和功能特别容易受到这些条件的影响。微结构WM变化，用扩散加权磁共振成像评估，已经可以在AD的临床前阶段检测到，在存在上述危险因素的情况下。特别是,边缘系统和皮质-皮质关联WM束，在大脑发育的后期髓鞘化，在最早的阶段退化。穹窿,起源于海马的C形WM束，是显示早期微观结构变化的边缘区域之一。Fornix完整性对于确保完整的执行功能和内存性能是必需的。因此，更好地了解导致穹窿变性的机制对于制定旨在预防高危人群认知功能下降的治疗策略至关重要.在这篇文献综述中，I)我们加深了这样一种观点，即部分丧失无礼完整性是AD的早期事件，ii）我们描述了AD的常见危险因素在穹窿变性中的作用，和iii）我们讨论了在脑血管疾病和炎症情况下WM变性的一些潜在的细胞和生理机制。
