Leyton Cristian E, Britton Anna K, Hodges John R, Halliday Glenda M, Kril Jillian J
Faculty of Health Sciences, The University of Sydney, Lidcombe, New South Wales, Australia; Neuroscience Research Australia, Randwick, New South Wales, Australia; ARC Centre of Excellence in Cognition and its Disorders, Sydney, New South Wales, Australia.
Department of Pathology, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Neurobiol Aging. 2016 Feb;38:82-92. doi: 10.1016/j.neurobiolaging.2015.10.017. Epub 2015 Oct 26.
Primary progressive aphasia (PPA) comprises a heterogeneous group of neurodegenerative conditions that can be classified in three cliniconeuroanatomic syndromes. Limited information exists, however, about patterns of neuropathologic spreading and microscopic changes underpinning each syndrome. We performed an analysis of a longitudinal in vivo cohort and a postmortem PPA cohort to investigate neurodegeneration over time and to quantify microscopic changes in key language brain areas. The longitudinal analyses demonstrated distinctive patterns of topological extension of brain atrophy. Although semantic variant (sv-PPA) showed an eccentric pattern, nonfluent and/or agrammatic (nfv-PPA) and logopenic (lv-PPA) variants showed additional multifocal extension. The quantitative pathology showed that sv-PPA had neuronal loss and thinning in BA 38, whereas nfv-PPA showed thinning in BA 44/45 and evidence of microscopic involvement in BA 40/22. Although lv-PPA showed neuronal loss focused on BA 40/22, imaging results demonstrated widespread left-sided brain atrophy. These analyses provide an account of the pathologic process whereby each variant has stereotypical patterns of brain atrophy extension, which is largely determined by the specific pathologic type.
原发性进行性失语（PPA）由一组异质性神经退行性疾病组成，可分为三种临床神经解剖综合征。然而，关于每种综合征背后的神经病理扩散模式和微观变化的信息有限。我们对一个纵向活体队列和一个死后PPA队列进行了分析，以研究随时间推移的神经退行性变，并量化关键语言脑区的微观变化。纵向分析显示了脑萎缩的独特拓扑扩展模式。虽然语义变异型（sv-PPA）表现出偏心模式，但非流利和/或语法缺失型（nfv-PPA）和音韵性变异型（lv-PPA）表现出额外的多灶性扩展。定量病理学显示，sv-PPA在BA 38有神经元丢失和变薄，而nfv-PPA在BA 44/45变薄，并有BA 40/22微观受累的证据。虽然lv-PPA显示神经元丢失集中在BA 40/22，但影像学结果显示左侧大脑广泛萎缩。这些分析说明了病理过程，即每种变异型都有典型的脑萎缩扩展模式，这在很大程度上由特定的病理类型决定。
