Evidence of cerebellar TDP-43 loss of function in FTLD-TDP.
Cerebellum
Frontotemporal lobar degeneration
Stathmin-2
TDP-43
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
25 07 2022
25 07 2022
Historique:
received:
16
05
2022
accepted:
11
07
2022
entrez:
25
7
2022
pubmed:
26
7
2022
medline:
28
7
2022
Statut:
epublish
Résumé
Frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) is a neurodegenerative disease primarily affecting the frontal and/or temporal cortices. However, a growing body of evidence suggests that the cerebellum contributes to biochemical, cognitive, and behavioral changes in FTLD-TDP. To evaluate cerebellar TDP-43 expression and function in FTLD-TDP, we analyzed TDP-43 protein levels and the splicing of a TDP-43 target, STMN2, in the cerebellum of 95 FTLD-TDP cases and 25 non-neurological disease controls. Soluble TDP-43 was decreased in the cerebellum of FTLD-TDP cases but a concomitant increase in insoluble TDP-43 was not seen. Truncated STMN2 transcripts, an indicator of TDP-43 dysfunction, were elevated in the cerebellum of FTLD-TDP cases and inversely associated with TDP-43 levels. Additionally, lower cerebellar TDP-43 associated with a younger age at disease onset. We provide evidence of TDP-43 loss of function in the cerebellum in FTLD-TDP, supporting further investigation into this understudied brain region.
Identifiants
pubmed: 35879741
doi: 10.1186/s40478-022-01408-6
pii: 10.1186/s40478-022-01408-6
pmc: PMC9310392
doi:
Substances chimiques
DNA-Binding Proteins
0
TARDBP protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
107Subventions
Organisme : NINDS NIH HHS
ID : R35 NS097273
Pays : United States
Organisme : NIH HHS
ID : U54NS123743
Pays : United States
Organisme : NIH HHS
ID : P01NS084974
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG063780
Pays : United States
Organisme : NIH HHS
ID : R01AG37491
Pays : United States
Organisme : NINDS NIH HHS
ID : P01 NS084974
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG037491
Pays : United States
Organisme : NIH HHS
ID : RF1NS120992
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS123743
Pays : United States
Organisme : NINDS NIH HHS
ID : RF1 NS120992
Pays : United States
Organisme : NIH HHS
ID : R01AG063780
Pays : United States
Organisme : NINDS NIH HHS
ID : R35NS097273
Pays : United States
Informations de copyright
© 2022. The Author(s).
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