Longitudinal Alzheimer's Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections
Longitudinal Alzheimer's Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections
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DOI：
10.1016/j.celrep.2018.06.001
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发表时间：
2018-07-03
期刊：
影响因子：
8.8
通讯作者：
Spreng, R. Nathan
中科院分区：
文献类型：
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作者：
Schmitz, Taylor W.;Mur, Marieke;Spreng, R. Nathan
基底前脑(BF)的胆碱能神经元几乎提供了大脑皮质和杏仁核的胆碱能输入。他们特别容易受到早期阿尔茨海默病(AD)的神经病理的影响，并可能通过胆碱能去神经和错误折叠的蛋白质跨突触扩散，在他们的皮质-杏仁核投射系统中触发神经病理的出现。我们研究了BF内的纵向变性是否可以解释AD神经病理的脑脊液生物标记物异常的老年人中的纵向皮质-杏仁核变性。我们专注于两个BF亚区，已知这两个亚区通过两个不同的宏观胆碱能投射来支配皮质-杏仁核区域。为了进一步评估AD患者这些区域的结构退化是否反映了胆碱能神经的丧失，我们使用了[F-18]FEOBV放射性示踪剂，它与皮质-杏仁核胆碱能终末结合。我们发现，这两个BF亚区解释了皮质-杏仁核退行性变在空间上的不同模式，这密切反映了它们的胆碱能投射，并与胆碱能失神经的[F-18]FEOBV指数重叠。
The cholinergic neurons of the basal forebrain (BF) provide virtually all of the brain's cortical and amygdalar cholinergic input. They are particularly vulnerable to neuropathology in early Alzheimer's disease (AD) and may trigger the emergence of neuropathology in their cortico-amygdalar projection system through cholinergic denervation and trans-synaptic spreading of misfolded proteins. We examined whether longitudinal degeneration within the BF can explain longitudinal cortico-amygdalar degeneration in older human adults with abnormal cerebrospinal fluid biomarkers of AD neuropathology. We focused on two BF subregions, which are known to innervate cortico-amygdalar regions via two distinct macroscopic cholinergic projections. To further assess whether structural degeneration of these regions in AD reflects cholinergic denervation, we used the [F-18] FEOBV radiotracer, which binds to cortico-amygdalar cholinergic terminals. We found that the two BF subregions explain spatially distinct patterns of cortico-amygdalar degeneration, which closely reflect their cholinergic projections, and overlap with [F-18] FEOBV indices of cholinergic denervation.