Plasma total prion protein as a potential biomarker for neurodegenerative dementia
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Plasma total prion protein as a potential biomarker for neurodegenerative dementia : diagnostic accuracy in the spectrum of prion diseases. / Llorens, F; Villar-Piqué, A; Schmitz, M; Diaz-Lucena, D; Wohlhage, M; Hermann, P; Goebel, S; Schmidt, I; Glatzel, M; Hauw, J-J; Sikorska, B; Liberski, P P; Riggert, J; Ferrer, I; Zerr, I.
in: NEUROPATH APPL NEURO, Jahrgang 46, Nr. 3, 04.2020, S. 240-254.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Plasma total prion protein as a potential biomarker for neurodegenerative dementia
T2 - diagnostic accuracy in the spectrum of prion diseases
AU - Llorens, F
AU - Villar-Piqué, A
AU - Schmitz, M
AU - Diaz-Lucena, D
AU - Wohlhage, M
AU - Hermann, P
AU - Goebel, S
AU - Schmidt, I
AU - Glatzel, M
AU - Hauw, J-J
AU - Sikorska, B
AU - Liberski, P P
AU - Riggert, J
AU - Ferrer, I
AU - Zerr, I
N1 - © 2019 British Neuropathological Society.
PY - 2020/4
Y1 - 2020/4
N2 - 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.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.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.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.
AB - 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.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.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.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.
U2 - 10.1111/nan.12573
DO - 10.1111/nan.12573
M3 - SCORING: Journal article
C2 - 31216593
VL - 46
SP - 240
EP - 254
JO - NEUROPATH APPL NEURO
JF - NEUROPATH APPL NEURO
SN - 0305-1846
IS - 3
ER -