Kerbler Georg M, Fripp Jürgen, Rowe Christopher C, Villemagne Victor L, Salvado Olivier, Rose Stephen, Coulson Elizabeth J
Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research, The University of Queensland, Brisbane, Qld 4072, Australia.
Commonwealth Scientific and Industrial Research Organisation, Computational Informatics, Brisbane, Qld 4029, Australia.
Neuroimage Clin. 2014 Nov 27;7:105-13. doi: 10.1016/j.nicl.2014.11.015. eCollection 2015.
The brains of patients suffering from Alzheimer's disease (AD) have three classical pathological hallmarks: amyloid-beta (Aβ) plaques, tau tangles, and neurodegeneration, including that of cholinergic neurons of the basal forebrain. However the relationship between Aβ burden and basal forebrain degeneration has not been extensively studied. To investigate this association, basal forebrain volumes were determined from magnetic resonance images of controls, subjects with amnestic mild cognitive impairment (aMCI) and AD patients enrolled in the longitudinal Alzheimer's Disease Neuroimaging Initiative (ADNI) and Australian Imaging, Biomarkers and Lifestyle (AIBL) studies. In the AIBL cohort, these volumes were correlated within groups to neocortical gray matter retention of Pittsburgh compound B (PiB) from positron emission tomography images as a measure of Aβ load. The basal forebrain volumes of AD and aMCI subjects were significantly reduced compared to those of control subjects. Anterior basal forebrain volume was significantly correlated to neocortical PiB retention in AD subjects and aMCI subjects with high Aβ burden, whereas posterior basal forebrain volume was significantly correlated to neocortical PiB retention in control subjects with high Aβ burden. Therefore this study provides new evidence for a correlation between neocortical Aβ accumulation and basal forebrain degeneration. In addition, cluster analysis showed that subjects with a whole basal forebrain volume below a determined cut-off value had a 7 times higher risk of having a worse diagnosis within ~18 months.
患有阿尔茨海默病（AD）的患者大脑具有三个典型的病理特征：β-淀粉样蛋白（Aβ）斑块、tau缠结和神经退行性变，包括基底前脑胆碱能神经元的神经退行性变。然而，Aβ负荷与基底前脑变性之间的关系尚未得到广泛研究。为了探究这种关联，我们从参与纵向阿尔茨海默病神经影像学计划（ADNI）和澳大利亚影像、生物标志物与生活方式（AIBL）研究的对照组、遗忘型轻度认知障碍（aMCI）受试者和AD患者的磁共振图像中确定了基底前脑体积。在AIBL队列中，将这些体积在组内与正电子发射断层扫描图像中匹兹堡化合物B（PiB）的新皮质灰质保留情况相关联，以此作为Aβ负荷的指标。与对照组相比，AD和aMCI受试者的基底前脑体积显著减小。在AD受试者和Aβ负荷高的aMCI受试者中，前基底前脑体积与新皮质PiB保留显著相关，而在Aβ负荷高的对照组受试者中，后基底前脑体积与新皮质PiB保留显著相关。因此，本研究为新皮质Aβ积累与基底前脑变性之间的相关性提供了新证据。此外，聚类分析表明，整个基底前脑体积低于确定临界值的受试者在约18个月内诊断恶化的风险高出7倍。
