Nucleus Basalis of Meynert (NbM), a crucial source of cholinergic projection to the entorhinal cortex (EC) and hippocampus (HC), has shown sensitivity to neurofibrillary degeneration in the early stages of Alzheimer’s Disease. Using deformation-based morphometry (DBM) on up-sampled MRI scans from 1447 Alzheimer’s Disease Neuroimaging Initiative participants, we aimed to quantify NbM degeneration along the disease trajectory. Results from cross-sectional analysis revealed significant differences of NbM volume between cognitively normal and early mild cognitive impairment cohorts, confirming recent studies suggesting that NbM degeneration happens before degeneration in the EC or HC. Longitudinal linear mixed-effect models were then used to compare trajectories of volume change after realigning all participants into a common timeline based on their cognitive decline. Results indicated the earliest deviations in NbM volumes from the cognitively healthy trajectory, challenging the prevailing idea that Alzheimer’s originates in the EC. Converging evidence from cross-sectional and longitudinal models suggest that the NbM may be a focal target of early AD progression, which is often obscured by normal age-related decline.

中文翻译：

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Meynert 基底核的变性标志着阿尔茨海默病进展的最早阶段

Meynert 基底核 (NbM) 是向内嗅皮层 (EC) 和海马体 (HC) 进行胆碱能投射的重要来源，在阿尔茨海默病的早期阶段，它对神经原纤维变性表现出敏感性。我们对 1447 名阿尔茨海默病神经影像计划参与者的上采样 MRI 扫描使用基于变形的形态测量 (DBM)，旨在量化沿疾病轨迹的 NbM 变性。横断面分析结果显示，认知正常组和早期轻度认知障碍组之间的 NbM 体积存在显着差异，证实了最近的研究表明 NbM 变性发生在 EC 或 HC 变性之前。然后，根据认知衰退将所有参与者重新调整到一个共同的时间线后，使用纵向线性混合效应模型来比较体积变化的轨迹。结果表明 NbM 量最早偏离认知健康轨迹，挑战了阿尔茨海默病起源于 EC 的普遍观点。来自横断面和纵向模型的综合证据表明，NbM 可能是早期 AD 进展的焦点目标，而这种进展常常被正常的年龄相关衰退所掩盖。