Tau immunotherapy is associated with glial responses in FTLD-tau.
Astrocyte
Astrocytic tau
Gosuranemab
Immunotherapy
Microglia
Tau
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
12
02
2021
accepted:
24
04
2021
revised:
23
04
2021
pubmed:
6
5
2021
medline:
14
1
2022
entrez:
5
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33950293
doi: 10.1007/s00401-021-02318-y
pii: 10.1007/s00401-021-02318-y
pmc: PMC8270872
mid: NIHMS1706127
doi:
Substances chimiques
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
243-257Subventions
Organisme : NIA NIH HHS
ID : P30 AG010124
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG017586
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG066597
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG063344
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG062418
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS115322
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072979
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS095793
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS109260
Pays : United States
Informations de copyright
© 2021. The Author(s).
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