Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neuropathologic subtypes of frontotemporal lobar degeneration with tau inclusions (FTLD-tau), primary tauopathies in which intracellular tau aggregation contributes to neurodegeneration. Gosuranemab (BIIB092) is a humanized monoclonal antibody that binds to N-terminal tau. While Gosuranemab passive immunotherapy trials for PSP failed to demonstrate clinical benefit, Gosuranemab reduced N-terminal tau in the cerebrospinal fluid of transgenic mouse models and PSP patients. However, the neuropathologic sequelae of Gosuranemab have not been described. In this present study, we examined the brain tissue of three individuals who received Gosuranemab. Post-mortem human brain tissues were studied using immunohistochemistry to identify astrocytic and microglial differences between immunized cases and a cohort of unimmunized PSP, CBD and aging controls. Gosuranemab immunotherapy was not associated with clearance of neuropathologic FTLD-tau inclusions. However, treatment-associated changes were observed including the presence of perivascular vesicular astrocytes (PVA) with tau accumulation within lysosomes. PVAs were morphologically and immunophenotypically distinct from the tufted astrocytes seen in PSP, granular fuzzy astrocytes (GFA) seen in aging, and astrocytic plaques seen in CBD. Additional glial responses included increased reactive gliosis consisting of bushy astrocytosis and accumulation of rod microglia. Together, these neuropathologic findings suggest that Gosuranemab may be associated with a glial response including accumulation of tau within astrocytic lysosomes.

进行性核上性麻痹 (PSP) 和皮质基底节变性 (CBD) 是带有 tau 包涵体 (FTLD-tau) 的额颞叶变性的神经病理学亚型，这是一种原发性 tau 病，其中细胞内 tau 聚集导致神经变性。Gosuranemab (BIIB092) 是一种结合 N 末端 tau 的人源化单克隆抗体。虽然针对 PSP 的 Gosuranemab 被动免疫治疗试验未能证明临床益处​​，但 Gosuranemab 减少了转基因小鼠模型和 PSP 患者脑脊液中的 N 末端 tau。然而，尚未描述 Gosuranemab 的神经病理学后遗症。在本研究中，我们检查了三个接受 Gosuranemab 治疗的个体的脑组织。使用免疫组织化学研究死后人脑组织，以确定免疫病例与未免疫 PSP、CBD 和衰老对照队列之间的星形胶质细胞和小胶质细胞差异。Gosuranemab 免疫疗法与神经病理学 FTLD-tau 包涵体的清除无关。然而，观察到与治疗相关的变化，包括血管周围囊泡星形胶质细胞 (PVA) 的存在以及溶酶体内的 tau 积累。PVA 在形态学和免疫表型上与 PSP 中看到的簇状星形胶质细胞、衰老中看到的颗粒状模糊星形胶质细胞 (GFA) 和 CBD 中看到的星形胶质细胞斑块不同。额外的神经胶质反应包括增加的反应性神经胶质增生，包括浓密的星形胶质细胞增多和杆状小胶质细胞的积累。一起，