Longitudinal in vivo imaging of synaptic pathologies of Alzheimer's disease

突触是神经系统的基本单位，使脑细胞和 为依赖经验的可塑性提供了一个基础，以驱动适应行为。改变...的力量 特定细胞或神经元群之间的突触被认为是更高大脑功能的基础，如 学习和记忆，而突触退化在许多神经病理中观察到，例如 阿尔茨海默病(AD)和相关的痴呆。尽管突触交流具有明显的意义，但 突触功能受损、阿尔茨海默病症状进展和认知功能下降之间的关系仍然存在 不清楚。然而，最近在分子显微镜方面的突破使人们能够直接成像人类免疫缺陷的进展。 阿尔茨海默病小鼠模型中的病理性突触缺陷。我们的方法是荧光标记 利用体内双光子技术跟踪突触蛋白和AD标记物在疾病发展过程中的作用 显微镜。通过对组成整个皮质和海马区回路的大量突触进行成像，我们 努力详细了解分子病理如何影响突触生理，并最终 会导致认知能力下降。这种方法将产生一个详细的时间进程的突触和 认知阿尔茨海默病可能揭示有效的治疗窗口和新的治疗途径 对人类疾病的干预。

The synapse is the fundamental unit of the nervous system, enabling communication between brain cells and providing a substrate for experience-dependent plasticity to drive adaptive behaviors. Altering the strength of synapses between specific cells or neuronal ensembles is thought to underlie higher brain functions such as learning and memory, whereas synaptic degradation is observed in many neurological pathologies, such as Alzheimer's disease (AD) and related dementias. Despite the clear significance of synaptic communication, the relationship between impaired synaptic function, progression of AD symptoms, and cognitive decline remains unclear. However, recent breakthroughs in molecular microscopy enable direct imaging of the progression of pathological synaptic deficits in mouse models of Alzheimer's disease. Our approach is to fluorescently tag synaptic proteins and AD markers to track them throughout disease progression using in vivo two-photon microscopy. By imaging large populations of synapses comprising entire cortical and hippocampal circuits, we strive to gain a detailed understanding of how molecular pathologies affect synaptic physiology and ultimately give rise to cognitive decline. This approach will yield a detailed time course of the progression of synaptic and cognitive Alzheimer's pathologies that may reveal effective treatment windows and novel avenues for therapeutic interventions for human disease.