Microstructural Neurodegeneration of the Entorhinal-Hippocampus Pathway along the Alzheimer's Disease Continuum.
Microstructural Neurodegeneration of the Entorhinal-Hippocampus Pathway along the Alzheimer's Disease Continuum.
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DOI：
10.3233/jad-230452
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发表时间：
2023
影响因子：
4
通讯作者：
Oishi, Kenichi
中科院分区：
文献类型：
--
作者：
Uchida, Yuto;Onda, Kengo;Hou, Zhipeng;Troncoso, Juan C.;Mori, Susumu;Oishi, Kenichi
关键词：
阿尔茨海默病(AD)神经退行性变的传统神经影像生物标志物不够敏感，无法检测AD患者临床前阶段的神经退行性改变。我们使用超高场扩散张量成像和体外脑组织的脑束造影术，检查了内嗅觉-海马区通路的神经退行性变是否可以沿着AD连续体被检测到。用11.7T弥散磁共振成像对1例无AD病变的认知正常个体(Non-AD)、1例认知正常的AD病变个体(临床期AD)和1例AD病变的痴呆个体(AD痴呆)的尸脑标本进行了扫描。比较不同AD连续体的内嗅层各向异性分数(FA值)和纤维束造影计数的穿支纤维数目。在影像分析之后，有髓纤维和神经细胞的状态通过随后的一系列组织学检查得到证实。在250μm(压缩至125μm)各向同性分辨率下，非阿尔茨海默病和临床前阿尔茨海默病患者均可辨认出内嗅II层岛和穿支纤维，而阿尔茨海默病患者则不能辨认，随后进行组织学验证。非AD组和临床前期AD组内嗅II层FA值最高，AD痴呆组内嗅II层FA值均匀较低。在AD连续体(非AD和GT；临床前AD 和GT； AD痴呆)中，FA值和穿支纤维数量减少。在AD的临床前阶段，我们成功地检测到了内嗅觉-海马区通路的神经退行性改变。
Conventional neuroimaging biomarkers for the neurodegeneration of Alzheimer’s disease (AD) are not sensitive enough to detect neurodegenerative alterations during the preclinical stage of AD individuals. We examined whether neurodegeneration of the entorhinal-hippocampal pathway could be detected along the AD continuum using ultra-high-field diffusion tensor imaging and tractography for ex vivo brain tissues. Postmortem brain specimens from a cognitively unimpaired individual without AD pathological changes (non-AD), a cognitively unimpaired individual with AD pathological changes (preclinical AD), and a demented individual with AD pathological changes (AD dementia) were scanned with an 11.7T diffusion magnetic resonance imaging. Fractional anisotropy (FA) values of the entorhinal layer II and number of perforant path fibers counted by tractography were compared among the AD continuum. Following the imaging analyses, the status of myelinated fibers and neuronal cells were verified by subsequent serial histological examinations. At 250μm (zipped to 125μm) isotropic resolution, the entorhinal layer II islands and the perforant path fibers could be identified in non-AD and preclinical AD, but not in AD dementia, followed by histological verification. The FA value of the entorhinal layer II was the highest among the entorhinal laminae in non-AD and preclinical AD, whereas the FA values in the entorhinal laminae were homogeneously low in AD dementia. The FA values and number of perforant path fibers decreased along the AD continuum (non-AD>preclinical AD > AD dementia). We successfully detected neurodegenerative alterations of the entorhinal-hippocampal pathway at the preclinical stage of the AD continuum.
影响因子：
3.7
作者：
Li Y;Shea SM;Lorenz CH;Jiang H;Chou MC;Mori S
通讯作者：
Mori S