Centre for Aging Brain and Neurodegenerative Disorder, Neurology Unit, University of Brescia, Brescia, Italy.
Neurobiol Aging. 2012 Oct;33(10):2506-20. doi: 10.1016/j.neurobiolaging.2011.10.031. Epub 2011 Nov 29.
Granulin (GRN) mutations have been identified as a major cause of frontotemporal lobar degeneration (FTLD) by haploinsufficiency mechanism, although their effects on brain tissue dysfunction and damage still remain to be clarified. In this study, we investigated the pattern of neuroimaging abnormalities in FTLD patients, carriers and noncarriers of GRN Thr272fs mutation, and in presymptomatic carriers. We assessed regional gray matter (GM) atrophy, and resting (RS)-functional magnetic resonance imaging (fMRI). The functional connectivity maps of the salience (SN) and the default mode (DMN) networks were considered. Frontotemporal gray matter atrophy was found in all FTLD patients (more remarkably in those GRN Thr272fs carriers), but not in presymptomatic carriers. Functional connectivity within the SN was reduced in all FTLD patients (again more remarkably in those mutation carriers), while it was enhanced in the DMN. Conversely, presymptomatic carriers showed increased connectivity in the SN, with no changes in the DMN. Our findings suggest that compensatory mechanisms of brain plasticity are present in GRN-related FTLD, but with different patterns at a preclinical and symptomatic disease stage.
颗粒体蛋白前体 (GRN) 突变通过杂合不足机制被鉴定为额颞叶痴呆 (FTLD) 的主要原因，尽管其对脑组织功能障碍和损伤的影响仍有待阐明。在这项研究中，我们研究了 FTLD 患者、GRN Thr272fs 突变携带者和非携带者以及无症状携带者的神经影像学异常模式。我们评估了区域性灰质 (GM) 萎缩和静息 (RS)-功能磁共振成像 (fMRI)。考虑了突显 (SN) 和默认模式 (DMN) 网络的功能连接图。所有 FTLD 患者都出现额颞叶灰质萎缩（GRN Thr272fs 携带者更为明显），但无症状携带者则没有。所有 FTLD 患者的 SN 内功能连接减少（突变携带者更为明显），而 DMN 内功能连接增加。相反，无症状携带者的 SN 连接增加，而 DMN 没有变化。我们的发现表明，GRN 相关 FTLD 存在大脑可塑性的代偿机制，但在临床前和症状期疾病阶段表现出不同的模式。
