Jacquemont Thomas, De Vico Fallani Fabrizio, Bertrand Anne, Epelbaum Stéphane, Routier Alexandre, Dubois Bruno, Hampel Harald, Durrleman Stanley, Colliot Olivier
Inserm, U1127, Paris, France; CNRS, UMR 7225 ICM, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, Paris, France; Inria, Aramis project-team, Centre de Recherche de Paris, France; Département de Biologie, Ecole normale supérieure, PSL Research University, F-75005, Paris, France.
Inserm, U1127, Paris, France; CNRS, UMR 7225 ICM, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, Paris, France; Inria, Aramis project-team, Centre de Recherche de Paris, France.
Neurobiol Aging. 2017 Jul;55:177-189. doi: 10.1016/j.neurobiolaging.2017.03.023. Epub 2017 Apr 5.
Alzheimer's disease (AD) is increasingly considered as a disconnection syndrome. Previous studies of the structural connectome in early AD stages have focused on mild cognitive impaired subjects (MCI), considering them as a homogeneous group. We studied 168 subjects from the Alzheimer's Disease Neuroimaging Initiative database (116 MCI and 52 cognitively normal subjects). Biomarker-based stratification using amyloid biomarkers (AV45 PET) and neurodegeneration biomarkers (MRI and FDG PET) led to 4 subgroups based on amyloid positivity (A+/-) and neurodegeneration positivity (N+/-): A-N-, A+N-, A-N+, and A+N+. Using diffusion MRI, we showed that both MCI A-N+ and MCI A+N+ subjects displayed an alteration of the white matter in the fornix and a significant bihemispheric network of decreased connections. These network alterations in MCI A+N+ are stronger and more focal than those of MCI A-N+. Only MCI A+N+ subjects exhibited specific changes in hippocampal connectivity and an AD-like alteration pattern. Our results indicate that the connectome disintegration pattern of MCI subgroups differ with respect to brain amyloid and neurodegeneration. Each of these 2 AD biomarkers induces a connectome alteration that is maximal when they coexist.
阿尔茨海默病（AD）越来越被视为一种连接障碍综合征。先前对早期AD阶段结构连接组的研究主要集中在轻度认知障碍受试者（MCI），将他们视为一个同质群体。我们研究了来自阿尔茨海默病神经影像倡议数据库的168名受试者（116名MCI受试者和52名认知正常受试者）。使用淀粉样蛋白生物标志物（AV45 PET）和神经退行性变生物标志物（MRI和FDG PET）进行基于生物标志物的分层，根据淀粉样蛋白阳性（A+/-）和神经退行性变阳性（N+/-）分为4个亚组：A-N-、A+N-、A-N+和A+N+。使用扩散MRI，我们发现MCI A-N+和MCI A+N+受试者均表现出穹窿白质改变以及显著的双侧半球连接减少网络。MCI A+N+中的这些网络改变比MCI A-N+的更强且更具局灶性。只有MCI A+N+受试者表现出海马连接的特定变化以及类似AD的改变模式。我们的结果表明，MCI亚组的连接组解体模式在脑淀粉样蛋白和神经退行性变方面存在差异。这两种AD生物标志物中的每一种都会诱发连接组改变，当它们共存时这种改变最大。
