Depletion of TDP-43 decreases fibril and plaque beta-amyloid and exacerbates neurodegeneration in an Alzheimer's mouse model
- Authors
- LaClair, Katherine D.; Donde, Aneesh; Ling, Jonathan P.; Jeong, Yun Ha; Chhabra, Resham; Martin, Lee J.; Wong, Philip C.
- Issue Date
- Dec-2016
- Publisher
- SPRINGER
- Keywords
- TDP-43; Alzheimer' s disease; beta-Amyloid; Nuclear depletion; Forebrain
- Citation
- ACTA NEUROPATHOLOGICA, v.132, no.6, pp.859 - 873
- Journal Title
- ACTA NEUROPATHOLOGICA
- Volume
- 132
- Number
- 6
- Start Page
- 859
- End Page
- 873
- URI
- http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/843
- DOI
- 10.1007/s00401-016-1637-y
- ISSN
- 0001-6322
- Abstract
- TDP-43 proteinopathy, initially associated with ALS and FTD, is also found in 30-60% of Alzheimer's disease (AD) cases and correlates with worsened cognition and neurodegeneration. A major component of this proteinopathy is depletion of this RNA-binding protein from the nucleus, which compromises repression of non-conserved cryptic exons in neurodegenerative diseases. To test whether nuclear depletion of TDP-43 may contribute to the pathogenesis of AD cases with TDP-43 proteinopathy, we examined the impact of depletion of TDP-43 in populations of neurons vulnerable in AD, and on neurodegeneration in an AD-linked context. Here, we show that some populations of pyramidal neurons that are selectively vulnerable in AD are also vulnerable to TDP-43 depletion in mice, while other forebrain neurons appear spared. Moreover, TDP-43 depletion in forebrain neurons of an AD mouse model exacerbates neurodegeneration, and correlates with increased prefibrillar oligomeric A beta and decreased A beta plaque burden. These findings support a role for nuclear depletion of TDP-43 in the pathogenesis of AD and provide strong rationale for developing novel therapeutics to alleviate the depletion of TDP-43 and functional antemortem biomarkers associated with its nuclear loss.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 연구본부 > 퇴행성 뇌질환 연구그룹 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/843)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.