Movement disorders are linked to TDP-43 burden in the substantia nigra of FTLD-TDP brain donors

Movement disorders (MD) have been linked to degeneration of the substantia nigra (SN) in Parkinson's disease and include bradykinesia, rigidity, and tremor. They are also present in frontotemporal dementia (FTD), where MD have been linked to frontotemporal lobar degeneration with tau pathology...

Full description

Saved in:

Bibliographic Details
Published in:	Acta neuropathologica communications Vol. 11; no. 1; p. 63
Main Authors:	Fiondella, Luigi, Gami-Patel, Priya, Blok, Christian A, Rozemuller, Annemieke J M, Hoozemans, Jeroen J M, Pijnenburg, Yolande A L, Scarioni, Marta, Dijkstra, Anke A
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 12-04-2023 BioMed Central BMC
Subjects:	Age Brain - pathology Brain donors Dementia DNA-Binding Proteins - metabolism Dystonia Frontotemporal Dementia Frontotemporal Dementia - pathology Frontotemporal Lobar Degeneration Frontotemporal Lobar Degeneration - pathology Humans Medical records Movement disorders Movement Disorders - pathology Neurons Parkinson's disease Pathology Substantia nigra Substantia Nigra - metabolism tau Proteins - metabolism TDP-43 Tremor (Muscular contraction) Netherlands Brain donors Frontotemporal Dementia Frontotemporal Lobar Degeneration Substantia nigra TDP-43 Movement disorders
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Movement disorders (MD) have been linked to degeneration of the substantia nigra (SN) in Parkinson's disease and include bradykinesia, rigidity, and tremor. They are also present in frontotemporal dementia (FTD), where MD have been linked to frontotemporal lobar degeneration with tau pathology (FTLD-tau). Although MD can also occur in FTLD with TDP-43 pathology (FTLD-TDP), the local pathology in the SN of FTLD-TDP patients with MD is currently unexplored. The aims of this study are to characterize the frequency and the nature of MD in a cohort of FTLD-TDP brain donors and to investigate the relationship between the presence of MD, the nigral neuronal loss, and the TDP-43 burden in the SN. From our cohort of FTLD-TDP patients (n = 53), we included 13 donors who presented with MD (FTLD-MD+), and nine age-sex matched donors without MD (FTLD-MD-) for whom the SN was available. In these donors, the TDP-43 burden and the neuronal density in the SN were assessed with ImageJ and Qupath software. The results were compared between the two groups using T-test. We found that the TDP-43 burden in the SN was higher in FTLD-MD+ (mean 3,43%, SD ± 2,7) compared to FTLD-MD- (mean 1,21%, SD ± 0,67) (p = 0,04), while no significant difference in nigral neuronal density was found between the groups (p = 0,09). 17% of FTLD-TDP patients developed MD, which present as symmetric akinetic-rigid parkinsonism or CBS. Given the absence of a significant nigral neuronal cell loss, TDP-43 induced neuronal dysfunction could be sufficient to cause MD.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2051-5960 2051-5960
DOI:	10.1186/s40478-023-01560-7