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Plasma total prion protein as a potential biomarker for neurodegenerative dementia: diagnostic accuracy in the spectrum of prion diseases.

Authors :
Llorens F
Villar-Piqué A
Schmitz M
Diaz-Lucena D
Wohlhage M
Hermann P
Goebel S
Schmidt I
Glatzel M
Hauw JJ
Sikorska B
Liberski PP
Riggert J
Ferrer I
Zerr I
Source :
Neuropathology and applied neurobiology [Neuropathol Appl Neurobiol] 2020 Apr; Vol. 46 (3), pp. 240-254. Date of Electronic Publication: 2019 Jul 19.
Publication Year :
2020

Abstract

Aims: In the search for blood-based biomarkers of neurodegenerative diseases, we characterized the concentration of total prion protein (t-PrP) in the plasma of neurodegenerative dementias. We aimed to assess its accuracy in this differential diagnostic context.<br />Methods: Plasma t-PrP was measured in 520 individuals including healthy controls (HC) and patients diagnosed with neurological disease control (ND), Alzheimer's disease (AD), sporadic Creutzfeldt-Jakob disease (sCJD), frontotemporal dementia (FTD), Lewy body dementia (LBD) and vascular dementia (VaD). Additionally, t-PrP was quantified in genetic prion diseases and iatrogenic CJD. The accuracy of t-PrP discriminating the diagnostic groups was evaluated and correlated with demographic, genetic and clinical data in prion diseases. Markers of blood-brain barrier impairment were investigated in sCJD brains.<br />Results: Compared to HC and ND, elevated plasma t-PrP concentrations were detected in sCJD, followed by FTD, AD, VaD and LBD. In sCJD, t-PrP was associated neither with age nor sex, but with codon 129 PRNP genotype. Plasma t-PrP concentrations correlated with cerebrospinal fluid (CSF) markers of neuro-axonal damage, but not with CSF t-PrP. In genetic prion diseases, plasma t-PrP was elevated in all type of mutations investigated. In sCJD brain tissue, extravasation of immunoglobulin G and the presence of swollen astrocytic end-feet around the vessels suggested leakage of blood-brain barrier as a potential source of increased plasma t-PrP.<br />Conclusions: Plasma t-PrP is elevated in prion diseases regardless of aetiology. This pilot study opens the possibility to consider plasma t-PrP as a promising blood-based biomarker in the diagnostic of prion disease.<br /> (© 2019 British Neuropathological Society.)

Details

Language :
English
ISSN :
1365-2990
Volume :
46
Issue :
3
Database :
MEDLINE
Journal :
Neuropathology and applied neurobiology
Publication Type :
Academic Journal
Accession number :
31216593
Full Text :
https://doi.org/10.1111/nan.12573