Early Alzheimer's Disease Neuropathology Detected by Proton MR Spectroscopy
Early Alzheimer's Disease Neuropathology Detected by Proton MR Spectroscopy
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DOI：
10.1523/jneurosci.2027-14.2014
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发表时间：
2014-12-03
影响因子：
5.3
通讯作者：
Kantarci, Kejal
中科院分区：
文献类型：
--
作者：
Murray, Melissa E.;Przybelski, Scott A.;Kantarci, Kejal
质子磁共振波谱（H-1-MRS）对与阿尔茨海默病（AD）相关的早期神经退行性过程敏感。虽然在扣带回后测量的n -乙酰天冬氨酸(NAA)/肌酸（Cr）、NAA/肌醇（mI）和mI/Cr的H-1-MRS代谢物比值揭示了AD疾病进展的证据，但AD中1H-MRS代谢物变化的病理基础尚不清楚。本研究纳入了经病理诊断的人类病例，从无可能性到高可能性AD （n = 41, 16名女性和25名男性），他们在死前接受了3特斯拉扣带回后H-1-MRS检查。使用突触小泡、过度磷酸化的tau蛋白（pTau）、神经原纤维缠结构象表位（cNFT）、β淀粉样蛋白、星形胶质细胞和小胶质细胞的抗体对后扣带回进行免疫组化评价。使用Aperio软件对载玻片进行数字分析，该软件允许对后扣带灰质进行神经病理学量化。根据从扫描到死亡的时间调整MRS和病理关联。在AD和对照组中，突触免疫反应性降低与扣带后回NAA/Cr和NAA/ml之间存在显著关联。较高的pTau负荷与较低的NAA/Cr和NAA/mI相关。较高的淀粉样蛋白负荷与较高的mI/Cr和较低的NAA/mI比值相关，但与NAA/Cr无关。H-1-MRS代谢物水平揭示与AD病理相关的早期神经退行性改变。我们的研究结果支持了NAA/Cr的降低与突触丢失和早期pTau病理相关的假设，但与后扣带回淀粉样蛋白- β或后来cNFT病理的积累无关。此外，mI/Cr升高与AD患者淀粉样蛋白斑块的发生有关。
Proton magnetic resonance spectroscopy (H-1-MRS) is sensitive to early neurodegenerative processes associated with Alzheimer's disease (AD). Although H-1-MRS metabolite ratios of N-acetyl aspartate (NAA)/creatine (Cr), NAA/myoinositol (mI), and mI/Cr measured in the posterior cingulate gyrus reveal evidence of disease progression in AD, pathologic underpinnings of the 1H-MRS metabolite changes in AD are unknown. Pathologically diagnosed human cases ranging from no likelihood to high likelihood AD (n = 41, 16 females and 25 males) who underwent antemortem H-1-MRS of the posterior cingulate gyrus at 3 tesla were included in this study. Immunohistochemical evaluation was performed on the posterior cingulate gyrus using antibodies to synaptic vesicles, hyperphosphorylated tau (pTau), neurofibrillary tangle conformational-epitope (cNFT), amyloid-beta, astrocytes, and microglia. The slides were digitally analyzed using Aperio software, which allows neuropathologic quantification in the posterior cingulate gray matter. MRS and pathology associations were adjusted for time from scan to death. Significant associations across AD and control subjects were found between reduced synaptic immunoreactivity and both NAA/Cr and NAA/ml in the posterior cingulate gyrus. Higher pTau burden was associated with lower NAA/Cr and NAA/mI. Higher amyloid-beta burden was associated with elevated mI/Cr and lower NAA/mI ratios, but not with NAA/Cr. H-1-MRS metabolite levels reveal early neurodegenerative changes associated with AD pathology. Our findings support the hypothesis that a decrease in NAA/Cr is associated with loss of synapses and early pTau pathology, but not with amyloid-beta or later accumulation of cNFT pathology in the posterior cingulate gyrus. In addition, elevation of mI/Cr is associated with the occurrence of amyloid-beta plaques in AD.