Sala-Llonch Roser, Lladó Albert, Fortea Juan, Bosch Beatriz, Antonell Anna, Balasa Mircea, Bargalló Nuria, Bartrés-Faz David, Molinuevo José Luis, Sánchez-Valle Raquel
Department of Psychiatry and Clinical Psychobiology, Universitat de Barcelona, Barcelona, Spain; Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, Barcelona, Spain.
Neurobiol Aging. 2015 Mar;36(3):1261-70. doi: 10.1016/j.neurobiolaging.2014.12.022. Epub 2014 Dec 24.
Familial Alzheimer's disease provides the opportunity to investigate brain changes even before the symptoms onset. We performed a structural magnetic resonance imaging (MRI) study in 38 participants from families with presenilin 1 gene mutations: 11 symptomatic mutation carriers, 13 asymptomatic mutation carriers (AMC), with a mean of 16.22 years before the estimated appearance of symptoms, and 14 noncarriers. A subset of subjects was studied longitudinally 2 and 4 years after the first scan. We found decreased cortical thickness (CTh) and volume in cortical and subcortical structures in symptomatic mutation carriers, with progressive loss over time. In AMC, we found increased CTh and volume in temporoparietal regions and in precuneus-posterior cingulate compared with controls at baseline. Longitudinal studies in AMC, by contrast, showed accelerated rates of CTh loss in precuneus-posterior cingulate and superior parietal, right lateral temporal and left orbitofrontal, and middle frontal regions. These findings suggest that brain structure in presenilin 1 mutation carriers follows nonlinear trajectories, with regional increases during the very early presymptomatic period. Initial neuroinflammation and/or accumulation of amyloid species followed by neurodegeneration, or congenital morphometric differences, may explain the observed features.
家族性阿尔茨海默病为在症状出现之前研究大脑变化提供了契机。我们对38名携带早老素1基因突变的家族成员进行了结构磁共振成像（MRI）研究：11名有症状的突变携带者，13名无症状突变携带者（AMC），其平均在估计症状出现前16.22年，以及14名非携带者。一部分受试者在首次扫描后2年和4年进行了纵向研究。我们发现有症状的突变携带者的皮质厚度（CTh）以及皮质和皮质下结构的体积减小，且随时间逐渐减少。在AMC中，与基线时的对照组相比，我们发现颞顶叶区域以及楔前叶-后扣带回的CTh和体积增加。相比之下，对AMC的纵向研究显示，楔前叶-后扣带回、顶上叶、右侧颞叶外侧、左侧眶额和额中回区域的CTh损失率加快。这些发现表明早老素1突变携带者的大脑结构遵循非线性轨迹，在症状出现前的极早期有区域增加。最初的神经炎症和/或淀粉样物质的积累随后导致神经退行性变，或先天性形态计量学差异，可能解释了观察到的特征。
