基底前脑活动可预测内嗅皮质的功能退化，并随阿尔茨海默病的进展而降低。
Basal forebrain activity predicts functional degeneration in the entorhinal cortex and decreases with Alzheimer's Disease progression.
作者信息
Mieling Marthe, Göttlich Martin, Yousuf Mushfa, Bunzeck Nico
机构信息
Department of Psychology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany.
Department of Neurology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany.
出版信息
bioRxiv. 2023 Mar 28:2023.03.28.534523. doi: 10.1101/2023.03.28.534523.
BACKGROUND AND OBJECTIVES
Recent models of Alzheimer's Disease (AD) suggest the nucleus basalis of Meynert (NbM) as the origin of structural degeneration followed by the entorhinal cortex (EC). However, the functional properties of NbM and EC regarding amyloid-β and hyperphosphorylated tau remain unclear.
METHODS
We analyzed resting-state (rs)fMRI data with CSF assays from the Alzheimer's Disease Neuroimaging Initiative (ADNI, n=71) at baseline and two years later.
RESULTS
At baseline, local activity, as quantified by fractional amplitude of low-frequency fluctuations (fALFF), differentiated between normal and abnormal CSF groups in the NbM but not EC. Further, NbM activity linearly decreased as a function of CSF ratio, resembling the disease status. Finally, NbM activity predicted the annual percentage signal change in EC, but not the reverse, independent from CSF ratio.
DISCUSSION
Our findings give novel insights into the pathogenesis of AD by showing that local activity in NbM is affected by proteinopathology and predicts functional degeneration within the EC.
背景与目的
近期的阿尔茨海默病（AD）模型表明，迈内特基底核（NbM）是结构退化的起源，随后是内嗅皮质（EC）。然而，关于淀粉样β蛋白和过度磷酸化tau蛋白，NbM和EC的功能特性仍不清楚。
方法
我们分析了来自阿尔茨海默病神经影像倡议（ADNI，n = 71）的静息态（rs）功能磁共振成像（fMRI）数据以及基线和两年后的脑脊液检测结果。
结果
在基线时，通过低频波动分数振幅（fALFF）量化的局部活动在NbM中区分了正常和异常脑脊液组，但在EC中没有。此外，NbM活动随脑脊液比率呈线性下降，类似于疾病状态。最后，NbM活动预测了EC中的年度百分比信号变化，但反之则不然，且与脑脊液比率无关。
讨论
我们的研究结果通过表明NbM中的局部活动受蛋白病理学影响并预测EC内的功能退化，为AD的发病机制提供了新的见解。
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