UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Differential patterns of lysosomal dysfunction are seen in the clinicopathological forms of primary progressive aphasia

Swift, Imogen J; Sjödin, Simon; Gobom, Johan; Brinkmalm, Ann; Blennow, Kaj; Zetterberg, Henrik; Rohrer, Jonathan D; (2023) Differential patterns of lysosomal dysfunction are seen in the clinicopathological forms of primary progressive aphasia. Journal of Neurology 10.1007/s00415-023-12063-9. (In press). Green open access

[thumbnail of s00415-023-12063-9.pdf]
Preview
Text
s00415-023-12063-9.pdf - Published Version

Download (999kB) | Preview

Abstract

Increasing evidence implicates endo-lysosomal dysfunction in frontotemporal dementia (FTD). 18 proteins were quantified using a mass spectrometry assay panel in the cerebrospinal fluid of 36 people with the language variant of FTD, primary progressive aphasia (PPA) (including 13 with non-fluent variant (nfvPPA), 11 with semantic variant (svPPA), and 12 with logopenic variant (lvPPA)) and 19 healthy controls. The concentrations of the cathepsins (B, D, F, L1, and Z) as well as AP-2 complex subunit beta, ganglioside GM2 activator, beta-hexosaminidase subunit beta, tissue alpha L-fucosidase, and ubiquitin were decreased in nfvPPA compared with controls. In contrast, the concentrations of amyloid beta A4 protein, cathepsin Z, and dipeptidyl peptidase 2 were decreased in svPPA compared with controls. No proteins were abnormal in lvPPA. These results indicate a differential alteration of lysosomal proteins in the PPA variants, suggesting those with non-Alzheimer’s pathologies are more likely to show abnormal lysosomal function.

Type: Article
Title: Differential patterns of lysosomal dysfunction are seen in the clinicopathological forms of primary progressive aphasia
Location: Germany
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s00415-023-12063-9
Publisher version: https://doi.org/10.1007/s00415-023-12063-9
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Frontotemporal dementia; Primary progressive aphasia; Endo-lysosomal proteins; Ubiquitin
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10180739
Downloads since deposit
12Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item