한빛사논문
- 조회431
Boram Kim1 · Bailey Mikytuck1 · Eunran Suh2 · Garrett S. Gibbons2 · Vivianna M. Van Deerlin2 · Sanjeev N. Vaishnavi3 · Meredith A. Spindler4 · Lauren Massimo5 · Murray Grossman5 · John Q. Trojanowski2 · David J. Irwin5 · Edward B. Lee1,*
1 Translational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, 613A Stellar Chance Laboratories, 422 Curie Blvd, Philadelphia, PA 19104, USA
2 Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
3 Penn Memory Center, Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
4 Parkinson’s Disease and Movement Disorders Center, Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
5 Penn Frontotemporal Degeneration Center, Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
*Corresponding author.
Abstract
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.
논문정보
- Research article
- 2021년 05월 (BRIC 등록일 2021-05-24)
- 국외 연구진
- 의약학 > 신경의학
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