Distinct molecular patterns of TDP-43 pathology in Alzheimer's disease: relationship with clinical phenotypes.
Alzheimer’s disease (AD)
Frontotemporal lobar degeneration (FTLD)
Phosphorylation
Protein aggregation
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:
29 04 2020
29 04 2020
Historique:
received:
13
04
2020
accepted:
15
04
2020
entrez:
1
5
2020
pubmed:
1
5
2020
medline:
1
6
2021
Statut:
epublish
Résumé
The co-existence of multiple pathologies and proteins is a common feature in the brains of cognitively impaired elderly individuals. Transactive response DNA-binding protein (TDP-43) has been discovered to accumulate in limbic brain regions of a portion of late-onset Alzheimer's disease (AD) patients, in addition to amyloid-β and τ protein. However, it is not yet known whether the TDP-43 species in the AD brain differ in their composition, when compared among different AD cases and to frontotemporal lobar degeneration cases with TDP-43 inclusions (FTLD-TDP). Furthermore, it is not known whether TDP-43 pathology in AD is related to symptoms of the frontotemporal dementia (FTD) spectrum. In this study, we investigated the molecular pattern of TDP-43 lesions with five different antibodies against different phosphorylated (pTDP-43) and non-phosphorylated TDP-43 epitopes. We analyzed a cohort of 97 autopsy cases, including brains from 20 non-demented individuals, 16 cognitively normal pathologically-defined preclinical AD (p-preAD), 51 neuropathologically-confirmed AD cases and 10 FTLD-TDP cases as positive controls. We observed distinct neuropathological patterns of TDP-43 among AD cases. In 11 neuropathologically-confirmed AD cases we found dystrophic neurites (DNs), neuronal cytoplasmic inclusions (NCIs) and/or neurofibrillary tangle (NFT)-like lesions not only positive for pTDP-43
Identifiants
pubmed: 32349792
doi: 10.1186/s40478-020-00934-5
pii: 10.1186/s40478-020-00934-5
pmc: PMC7189555
doi:
Substances chimiques
DNA-Binding Proteins
0
TARDBP protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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