Plasma and cerebrospinal fluid tau and neurofilament concentrations in rapidly progressive neurological syndromes: a neuropathology‐based cohort

Kovács, Gábor G.; Andréasson, Ulf; Liman, Victor; Regelsberger, Günther; Lutz, Mirjam I.; Danics, Krisztina; Keller, Éva; Zetterberg, Henrik; Blennow, Kaj

doi:10.1111/ene.13389

Cited by 78 publications

(107 citation statements)

References 50 publications

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“…Thus, if data on PRNP polymorphism are available, which is a routine test in prion diagnostic centres, plasma t‐PrP may be a fast, accurate, robust and informative front‐line test in order to facilitate an initial screening in the diagnosis of prion disease, especially if combined with other emerging blood‐based prion biomarkers such as total‐tau and neurofilament light (NFL) . However, it is worth mentioning that neither total‐tau nor NFL has been systematically scrutinized for its differential diagnostic value in other neurodegenerative dementias, although in blood, elevated concentrations of both biomarkers have been detected in AD , FTD and in rapidly progressive dementias from different aetiologies . Indeed, the mechanisms underlying the presence of t‐PrP in blood must be different from those behind the other two biomarkers.…”

Section: Discussionmentioning

confidence: 99%

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

Llorens

Villar‐Piqué²,

Schmitz

et al. 2019

Neuropathology Appl Neurobio

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2020) Neuropathology and Applied Neurobiology 46, 240-254 Plasma total prion protein as a potential biomarker for neurodegenerative dementia: diagnostic accuracy in the spectrum of prion diseases 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.

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Section: Discussionmentioning

confidence: 99%

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

Llorens

Villar‐Piqué²,

Schmitz

et al. 2019

Neuropathology Appl Neurobio

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“…Twelve studies compared blood (i.e., plasma and serum) NfL concentration in AD cases and cognitively unimpaired controls [4,9,25,30,42,[47][48][49][50][51][52][53]; however, three of these studies used largely overlapping data from the ADNI database [49,50,53]. To avoid bias, the largest of the three overlapping studies was selected for inclusion in the meta-analysis [53]; thus, 10 studies comparing 471 AD cases to 518 cognitively unimpaired controls were included in the meta-analysis.…”

Section: Nfl In Admentioning

confidence: 99%

“…2D). Of these studies, 5 studies (365 AD cases and 357 cognitively unimpaired controls) compared NfL concentration in plasma, with an average ratio of 2.11 (95% CI 0.78-5.73) [25,30,47,48,53]. The remaining 5 studies (106 AD cases and 161 cognitively unimpaired controls) compared serum NfL concentration [4,9,42,51,52], with an average ratio of 3.22 (95% CI 1.37-7.57).…”

Section: Nfl In Admentioning

confidence: 99%

The diagnostic performance of neurofilament light chain in CSF and blood for Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis: A systematic review and meta‐analysis

Forgrave

Huei‐Ming

Best

et al. 2019

Alz & Dem Diag Ass & Dis Mo

126

134

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Introduction A systematic review and meta‐analysis was performed regarding the diagnostic performance of neurofilament light chain (NfL) in CSF and blood. Methods A database search was conducted for NfL biomarker studies in the context of Alzheimer's disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) compared with controls (i.e., cognitively unimpaired, mild cognitive impairment, or disease mimics). Results In groups with a sufficient number of studies, the performance of NfL in blood and CSF was similar. Compared with disease mimics, we observed that CSF NfL had strong discriminatory power for ALS, modest discriminatory power for FTD, and no discriminatory power for AD. NfL provided the greatest separation between ALS and cognitively unimpaired controls in both the blood and CSF, followed by FTD (CSF and blood), then AD (blood and CSF). Discussion Comparable performance of CSF and blood NfL in many groups demonstrates the promise of NfL as a noninvasive biomarker of neurodegeneration; however, its utility in clinically meaningful scenarios requires greater scrutiny. Toward clinical implementation, a more comprehensive understanding of NfL concentrations in disease subtypes with overlapping phenotypes and at defined stages of disease, and the development of a harmonization program, are warranted.

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“…Indeed, concentrations of plasma NFL, a protein abundant in large caliber myelinated axons, are significantly increased during neurodegeneration. Overall, growing data from ALS studies [17], PD, and atypical parkinsonism [18], such as progressive supranuclear palsy, AD [15], FTD [19], Huntington disease [20], and Creutzfeld-Jacob disease [21] involving different centers and cohortsshowed a good diagnostic accuracy in differentiating NDD patients from controls, starting from the early stages of neurodegeneration [22]. Increased NFL concentrations during the initial phases of ALS indicate a poor prognosis regarding symptom progression and survival of patients [17].…”

Section: Ultrasensitive Technologies For Peripheral Biomarkers Quantimentioning

confidence: 99%

A frontline defense against neurodegenerative diseases:the development of early disease detection methods

Baldacci

Lista

Vergallo

et al. 2019

Expert Review of Molecular Diagnostics

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Plasma and cerebrospinal fluid tau and neurofilament concentrations in rapidly progressive neurological syndromes: a neuropathology‐based cohort

Cited by 78 publications

References 50 publications

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

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

The diagnostic performance of neurofilament light chain in CSF and blood for Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis: A systematic review and meta‐analysis

A frontline defense against neurodegenerative diseases:the development of early disease detection methods

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