Université Paris-Saclay, UNIACT, NeuroSpin, CEA, Gif-sur-Yvette, France.
Université Paris-Saclay, BioMaps, Service Hospitalier Frédéric Joliot, CEA, CNRS, Inserm, Orsay, France.
Alzheimers Dement. 2024 Oct;20(10):6922-6934. doi: 10.1002/alz.14156. Epub 2024 Aug 28.
Typical Alzheimer's disease (AD) and limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE) are two neurodegenerative diseases that present with a similar initial amnestic clinical phenotype but are associated with distinct proteinopathies.
We investigated white matter (WM) fiber bundle alterations, using fixel-based analysis, a state-of-the-art diffusion magnetic resonance imaging model, in early AD, presumed LATE, and controls. We also investigated regional cortical atrophy.
Both amnestic AD and presumed LATE patients exhibited WM alterations in tracts of the temporal and limbic lobes and in callosal fibers connecting superior frontal gyri. In addition, presumed LATE patients showed alterations in callosal fibers connecting the middle frontal gyri and in the cerebello-thalamo-cortical tract. Cortical thickness was reduced in regions connected by the most altered tracts.
These findings, the first to describe WM fiber bundle alterations in presumed LATE, are consistent with results on cortical atrophy and with the staging system of tau or TDP-43 accumulation.
Fixel-based analysis revealed white matter (WM) fiber bundle alterations in presumed limbic-predominant age-related TAR DNA-binding protein 43 encephalopathy (LATE) patients identified by isolated episodic/limbic amnesia, the absence of positive Alzheimer's disease (AD) biomarkers, and no other neurological diagnosis after 2 years of follow-up. Presumed LATE and amnestic AD shared similar patterns of WM alterations in fiber bundles of the limbic and temporal lobes, in congruence with their similar limbic cognitive phenotype. Presumed LATE differed from AD by the alteration of the callosal fibers connecting the middle frontal gyri and of the cerebello-thalamo-cortical tract. WM fiber bundle alterations were consistent with results on regional cortical atrophy. The different anatomical patterns of WM degeneration could provide information on the propagation pathways of distinct proteinopathies.
典型的阿尔茨海默病（AD）和以边缘系统为主的与年龄相关的 TAR DNA 结合蛋白 43（TDP-43）脑病（LATE）是两种神经退行性疾病，它们具有相似的初始遗忘临床表型，但与不同的蛋白病变有关。
我们使用基于固定体的分析（一种最先进的扩散磁共振成像模型）研究了早期 AD、假定的 LATE 和对照组的白质（WM）纤维束改变。我们还研究了区域性皮质萎缩。
遗忘型 AD 和假定的 LATE 患者的颞叶和边缘叶以及连接额上回的胼胝体纤维的 WM 均发生改变。此外，假定的 LATE 患者的额中回之间的胼胝体纤维和小脑-丘脑-皮质束发生改变。改变最严重的区域的皮质厚度降低。
这些发现首次描述了假定的 LATE 中的 WM 纤维束改变，与皮质萎缩的结果以及 Tau 或 TDP-43 积累的分期系统一致。
基于固定体的分析显示，在孤立的发作性/边缘性遗忘、缺乏阳性阿尔茨海默病（AD）生物标志物且在 2 年随访后无其他神经诊断的假定的边缘性为主的与年龄相关的 TAR DNA 结合蛋白 43 脑病（LATE）患者中，发现了白质（WM）纤维束改变。假定的 LATE 和遗忘型 AD 在边缘和颞叶纤维束中具有相似的 WM 改变模式，与其相似的边缘认知表型一致。假定的 LATE 与 AD 的不同之处在于连接额中回的胼胝体纤维和小脑-丘脑-皮质束的改变。WM 纤维束改变与区域性皮质萎缩的结果一致。不同的 WM 退化解剖模式可以提供有关不同蛋白病变传播途径的信息。
