Youssef Hossam, Gatto Rodolfo G, Pham Nha Trang Thu, Jones David, Petersen Ronald C, Machulda Mary M, Whitwell Jennifer L, Josephs Keith A
Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Neuropathology. 2025 Feb 20. doi: 10.1111/neup.70000.
Alzheimer's disease (AD) is the leading cause of dementia in the elderly, marked by abnormal protein buildup (beta-amyloid and tau) resulting in neuronal loss, especially in the medial temporal lobe and other limbic regions. The presence of transactive response DNA binding protein 43 (TDP-43) immunoreactive inclusions in medial temporal lobe regions has also been associated with neuroimaging changes in limbic regions. It has been proposed that hypometabolism in limbic regions on [F] fluorodeoxyglucose positron emission tomography (FDG-PET) in a patient with a slowly evolving amnestic syndrome may be a signature of the presence of TDP-43. In this context, we observed an 86-year-old Caucasian female with dementia characterized by a slowly evolving amnestic syndrome, along with focal medial temporal atrophy evident on MRI and hypometabolism in limbic regions on FDG-PET. The patient subsequently died and underwent an autopsy. We performed detailed neuroimaging and digital neuropathological analyses of the hippocampal subfields to better understand the relationship between clinico-imaging findings and histopathology. In addition to TDP-43, we identified three other pathological processes in the medial temporal lobe: sequestosome-1/p62, argyrophilic grain disease (AGD), and primary age-related tauopathy (PART). Hippocampal subfield volumes and rates of atrophy were no different from those of matched healthy controls, except for the atrophy rate in cornu ammonis 1 (CA1). Digital histopathology revealed the relative highest burden of pathology for p62, followed by TDP-43, AGD, and PART in CA1. Multiple pathological processes appear to have contributed to the hippocampal atrophy and hypometabolism in our patient with a slowly progressive amnestic syndrome.
阿尔茨海默病（AD）是老年人痴呆的主要病因，其特征是异常蛋白质积聚（β-淀粉样蛋白和tau蛋白）导致神经元丢失，尤其是在内侧颞叶和其他边缘区域。内侧颞叶区域存在反式激活应答DNA结合蛋白43（TDP-43）免疫反应性包涵体也与边缘区域的神经影像学改变有关。有人提出，在患有缓慢进展性遗忘综合征的患者中，[F]氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）显示的边缘区域代谢减低可能是TDP-43存在的标志。在此背景下，我们观察了一名86岁的白种女性痴呆患者，其特征为缓慢进展性遗忘综合征，MRI显示局灶性内侧颞叶萎缩，FDG-PET显示边缘区域代谢减低。该患者随后死亡并接受了尸检。我们对海马亚区进行了详细的神经影像学和数字神经病理学分析，以更好地了解临床影像学表现与组织病理学之间的关系。除了TDP-43，我们在内侧颞叶还发现了其他三种病理过程：聚集体蛋白1/p62、嗜银颗粒病（AGD）和原发性年龄相关tau病（PART）。海马亚区体积和萎缩率与匹配的健康对照无差异，但海马1角（CA1）的萎缩率除外。数字组织病理学显示，CA1区p62的病理负担相对最高，其次是TDP-43、AGD和PART。多种病理过程似乎导致了我们这位患有缓慢进展性遗忘综合征患者的海马萎缩和代谢减低。
