Pini Lorenzo, Wennberg Alexandra M, Salvalaggio Alessandro, Vallesi Antonino, Pievani Michela, Corbetta Maurizio
Department of Neuroscience and Padova Neuroscience Center, University of Padova, Italy.
Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Ageing Res Rev. 2021 Dec;72:101482. doi: 10.1016/j.arr.2021.101482. Epub 2021 Oct 2.
Alzheimer's disease (AD) is characterized by different clinical entities. Although AD phenotypes share a common molecular substrate (i.e., amyloid beta and tau accumulation), several clinicopathological differences exist. Brain functional networks might provide a macro-scale scaffolding to explain this heterogeneity. In this review, we summarize the evidence linking different large-scale functional network abnormalities to distinct AD phenotypes. Specifically, executive deficits in early-onset AD link with the dysfunction of networks that support sustained attention and executive functions. Posterior cortical atrophy relates to the breakdown of visual and dorsal attentional circuits, while the primary progressive aphasia variant of AD may be associated with the dysfunction of the left-lateralized language network. Additionally, network abnormalities might provide in vivo signatures for distinguishing proteinopathies that mimic AD, such as TAR DNA binding protein 43 related pathologies. These network differences vis-a-vis clinical syndromes are more evident in the earliest stage of AD. Finally, we discuss how these findings might pave the way for new tailored interventions targeting the most vulnerable brain circuit at the optimal time window to maximize clinical benefits.
阿尔茨海默病（AD）具有不同的临床类型。尽管AD的表型具有共同的分子基础（即β淀粉样蛋白和tau蛋白积累），但仍存在一些临床病理差异。脑功能网络可能提供一个宏观框架来解释这种异质性。在本综述中，我们总结了将不同的大规模功能网络异常与不同AD表型联系起来的证据。具体而言，早发性AD中的执行功能缺陷与支持持续注意力和执行功能的网络功能障碍有关。后皮质萎缩与视觉和背侧注意力回路的破坏有关，而AD的原发性进行性失语变体可能与左侧化语言网络的功能障碍有关。此外，网络异常可能为区分模仿AD的蛋白病（如TAR DNA结合蛋白43相关病理）提供体内特征。这些网络差异与临床综合征在AD的最早阶段更为明显。最后，我们讨论了这些发现如何为新的针对性干预措施铺平道路，即在最佳时间窗口针对最脆弱的脑回路，以最大化临床益处。
