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

摘要

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.