Patterns of TDP-43 Deposition in Brains with LRRK2 G2019S Mutations.
LRRK2
TDP-43
neuropathology
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
09
03
2023
received:
24
05
2022
accepted:
01
05
2023
pmc-release:
01
08
2024
medline:
14
8
2023
pubmed:
23
5
2023
entrez:
23
5
2023
Statut:
ppublish
Résumé
To assess for TDP-43 deposits in brains with and without a LRRK2 G2019S mutation. LRRK2 G2019S mutations have been associated with parkinsonism and a wide range of pathological findings. There are no systematic studies examining the frequency and extent of TDP-43 deposits in neuropathological samples from LRRK2 G2019S carriers. Twelve brains with LRRK2 G2019S mutations were available for study from the New York Brain Bank at Columbia University; 11 of them had samples available for TDP-43 immunostaining. Clinical, demographic, and pathological data are reported for 11 brains with a LRRK2 G2019S mutation and compared to 11 brains without GBA1 or LRRK2 G2019S mutations with a pathologic diagnosis of Parkinson's disease (PD) or diffuse Lewy body disease. They were frequency matched by age, gender, parkinsonism age of onset, and disease duration. TDP-43 aggregates were present in 73% (n = 8) of brains with a LRRK2 mutation and 18% (n = 2) of brains without a LRRK2 mutation (P = 0.03). In one brain with a LRRK2 mutation, TDP-43 proteinopathy was the primary neuropathological change. Extranuclear TDP-43 aggregates are observed with greater frequency in LRRK2 G2019S autopsies compared to PD cases without a LRRK2 G2019S mutation. The association between LRRK2 and TDP-43 should be further explored. © 2023 International Parkinson and Movement Disorder Society.
Sections du résumé
OBJECTIVE
To assess for TDP-43 deposits in brains with and without a LRRK2 G2019S mutation.
BACKGROUND
LRRK2 G2019S mutations have been associated with parkinsonism and a wide range of pathological findings. There are no systematic studies examining the frequency and extent of TDP-43 deposits in neuropathological samples from LRRK2 G2019S carriers.
METHODS
Twelve brains with LRRK2 G2019S mutations were available for study from the New York Brain Bank at Columbia University; 11 of them had samples available for TDP-43 immunostaining. Clinical, demographic, and pathological data are reported for 11 brains with a LRRK2 G2019S mutation and compared to 11 brains without GBA1 or LRRK2 G2019S mutations with a pathologic diagnosis of Parkinson's disease (PD) or diffuse Lewy body disease. They were frequency matched by age, gender, parkinsonism age of onset, and disease duration.
RESULTS
TDP-43 aggregates were present in 73% (n = 8) of brains with a LRRK2 mutation and 18% (n = 2) of brains without a LRRK2 mutation (P = 0.03). In one brain with a LRRK2 mutation, TDP-43 proteinopathy was the primary neuropathological change.
CONCLUSIONS
Extranuclear TDP-43 aggregates are observed with greater frequency in LRRK2 G2019S autopsies compared to PD cases without a LRRK2 G2019S mutation. The association between LRRK2 and TDP-43 should be further explored. © 2023 International Parkinson and Movement Disorder Society.
Identifiants
pubmed: 37218402
doi: 10.1002/mds.29449
pmc: PMC10524857
mid: NIHMS1899906
doi:
Substances chimiques
DNA-Binding Proteins
0
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
EC 2.7.11.1
LRRK2 protein, human
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
TARDBP protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1541-1545Subventions
Organisme : NIA NIH HHS
ID : P50 AG008702
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066462
Pays : United States
Informations de copyright
© 2023 International Parkinson and Movement Disorder Society.
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