Cytopathology, Graduate School of Medical Sciences, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0373, Japan.
Cytopathology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0373, Japan.
Ann Nucl Med. 2024 Feb;38(2):120-130. doi: 10.1007/s12149-023-01879-0. Epub 2023 Nov 3.
2-[F]fluoro-2-deoxy-D-glucose positron emission tomography ([F]-FDG-PET) is a imaging modality that has been used to measure of glucose metabolism in the brain in Alzheimer's disease (AD). Clinically, decreased glucose uptake has been reported in the brain of AD, although the precise underlying mechanisms have not yet been elucidated. To elucidate the mechanisms of decreased [F]-FDG uptake in the AD by PET, [F]-FDG uptake in the brain of aged model mouse of AD was investigated using a dynamic autoradiography technique "bioradiography". A X-ray phase-contrast imaging (X-PCI) and a histopathological evaluation were also investigated to elucidate the mechanisms underlying the relationships between decreased [F]-FDG uptake and the pathological changes in the brain of AD mouse.
In this study, AD model mouse (5XFAD, APP/PS1) were used. [F]-FDG-bioradiography was conducted in fresh slices of brain tissue under the condition of resting (slices immersed in 5 mM K solution) and metabolically active (in 50 mM K solution). Amyloid β42 (Aβ42) deposition in the brain of AD mouse was confirmed by X-PCI. In addition, the positive cells of phosphated tau protein (P-tau) and deposition of Aβ42 were also examined by immunohistochemical staining.
No significant differences were observed between the two groups in the resting condition. In the activate condition of the brain, [F]-FDG uptake was significantly decreased in AD mice compared to WT mice. In X-PCI showed Aβ deposition in the AD mouse, but not in the WT. The AD mouse also showed increased P-tau, accumulation of Aβ42, increase in neuronal apoptosis, and decrease in the number of neurons than that of the WT mouse.
Neuronal damage, and induction of neuronal apoptosis, decreased [F]-FDG uptake, increased Aβ accumulation and P-tau induced neurofibrillary degeneration are observed in AD mouse. In clinical diagnosis, reduction of [F]-FDG uptake by PET is one of the means of diagnosing the onset of AD. Our results suggest that decreased uptake of [F]-FDG in the brains of AD may be associated with neuronal dysfunction and cell death in the brain.
2-[F]氟代-2-脱氧-D-葡萄糖正电子发射断层扫描([F]-FDG-PET)是一种已用于测量阿尔茨海默病(AD)大脑中葡萄糖代谢的成像方式。临床上，已经报道 AD 患者大脑中的葡萄糖摄取减少，尽管尚未阐明确切的潜在机制。为了通过 PET 阐明 AD 中[F]-FDG 摄取减少的机制，使用动态放射自显影技术“生物放射自显影”研究了 AD 年龄模型小鼠大脑中的[F]-FDG 摄取。还研究了 X 射线相衬成像(X-PCI)和组织病理学评估，以阐明 AD 小鼠大脑中[F]-FDG 摄取减少与病理变化之间关系的潜在机制。
本研究使用 AD 模型小鼠(5XFAD，APP/PS1)。在休息状态(切片浸入 5 mM K 溶液中)和代谢活跃状态(在 50 mM K 溶液中)下，在脑组织新鲜切片中进行[F]-FDG 生物放射自显影。通过 X-PCI 证实 AD 小鼠大脑中的β淀粉样蛋白 42(Aβ42)沉积。此外，还通过免疫组织化学染色检查磷酸化 tau 蛋白(P-tau)的阳性细胞和 Aβ42 的沉积。
在休息状态下，两组之间没有观察到显著差异。在大脑的激活状态下，与 WT 小鼠相比，AD 小鼠的[F]-FDG 摄取明显减少。在 X-PCI 中显示 AD 小鼠存在 Aβ 沉积，但 WT 小鼠不存在。与 WT 小鼠相比，AD 小鼠还表现出 P-tau 增加、Aβ42 积累、神经元凋亡增加和神经元数量减少。
在 AD 小鼠中观察到神经元损伤、神经元凋亡诱导、[F]-FDG 摄取减少、Aβ 积累增加和 P-tau 诱导的神经纤维变性。在临床诊断中，PET 中[F]-FDG 摄取的减少是诊断 AD 发病的手段之一。我们的结果表明，AD 患者大脑中[F]-FDG 摄取减少可能与大脑中的神经元功能障碍和细胞死亡有关。
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