Department of Radiology, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan.
Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan.
J Alzheimers Dis. 2024 Nov;102(1):228-236. doi: 10.1177/13872877241284314. Epub 2024 Oct 17.
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β and tau proteins, leading to neurofibrillary tangles. A biomarker-based diagnostic method called the ATN system categorizes AD pathology into amyloid-β (A), tau (T), and neurodegeneration (N). The relationship between regional tau deposition and reduced glucose metabolism in the preclinical AD stage is not well understood.
We presented voxel-by-voxel metabolic/tau deposition ratio (MTR) images to investigate the effects of tau deposition on metabolism in AD brains on a stage-by-stage basis.
We selected 174 subjects who underwent 3D-MRI, FDG-PET, amyloid PET, and tau PET scans. MTR images were created by normalizing FDG-PET toMK6240 PET images. Voxel-wise comparisons among 63 cognitively normal amyloid-negative (CNA) subjects, 49 subjects with AD dementia (ADD), 23 subjects with mild cognitive impairment due to AD (MCA), and 39 preclinical AD (PRC) subjects were conducted.
There was reduced glucose metabolism in ADD and MCA groups compared to CNA, predominantly in parietotemporal areas. Tau deposition was observed in wider areas in ADD and restricted to the medial temporal lobes in MCA. MTR exhibited significant reductions in broader regions in ADD and MCA, indicating simultaneous glucose metabolism decrease and tau deposition. At the MCA and PRC stages, glucose metabolism impairment and tau deposition were shown in separate regions by FDG PET and tau PET, respectively, while MTR images showed impairment in both regions.
Our findings suggest that MTR imaging provides insights into AD pathophysiology by simultaneously assessing glucose metabolism and tau deposition. In the early stage of the AD continuum (MCA and PRC), metabolic decline and tau deposition occur independently in different brain regions.
阿尔茨海默病（AD）的特征是淀粉样蛋白-β和 tau 蛋白的积累，导致神经原纤维缠结。一种基于生物标志物的诊断方法称为 ATN 系统，将 AD 病理学分为淀粉样蛋白-β（A）、tau（T）和神经退行性变（N）。在 AD 的临床前阶段，tau 沉积与葡萄糖代谢减少之间的关系尚未得到很好的理解。
我们提出了基于体素的代谢/tau 沉积比（MTR）图像，以研究 tau 沉积对 AD 大脑代谢的分期影响。
我们选择了 174 名接受 3D-MRI、FDG-PET、淀粉样蛋白 PET 和 tau PET 扫描的受试者。MTR 图像是通过将 FDG-PET 与 MK6240 PET 图像进行标准化而创建的。在 63 名认知正常、淀粉样蛋白阴性（CNA）的受试者、49 名 AD 痴呆（ADD）受试者、23 名 AD 导致的轻度认知障碍（MCA）受试者和 39 名临床前 AD（PRC）受试者中进行了基于体素的比较。
ADD 和 MCA 组与 CNA 相比，葡萄糖代谢减少，主要在前颞叶区域。ADD 组 tau 沉积面积较广，MCA 组局限于内侧颞叶。ADD 和 MCA 组的 MTR 显示更广泛区域的显著减少，表明葡萄糖代谢减少和 tau 沉积同时发生。在 MCA 和 PRC 阶段，FDG-PET 和 tau PET 分别显示葡萄糖代谢损伤和 tau 沉积在不同区域，而 MTR 图像显示两个区域均有损伤。
我们的研究结果表明，MTR 成像通过同时评估葡萄糖代谢和 tau 沉积，为 AD 病理生理学提供了深入了解。在 AD 连续体的早期阶段（MCA 和 PRC），代谢下降和 tau 沉积发生在不同的脑区。
