Neurofilament light chain as a blood biomarker to differentiate psychiatric disorders from behavioural variant frontotemporal dementia

Shweiki, Mhd Rami Al; Steinacker, Petra; Oeckl, Patrick; Hengerer, Bastian; Danek, Adrian; Faßbender, Klaus; Diehl‐Schmid, Janine; Jahn, Holger; Anderl‐Straub, Sarah; Ludolph, Albert C.; Schönfeldt‐Lecuona, Carlos; Otto, Markus

doi:10.1016/j.jpsychires.2019.03.019

Cited by 91 publications

(76 citation statements)

References 16 publications

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“…The fact that the phenotypes under the FTLD spectrum show a significant clinical overlap with psychiatric disorders [1][2][3], but substantially differ in the underlying pathophysiology, highlights the importance of minimally invasive pathophysiological biomarkers differentiating these two etiologies. In this present study, we have shown that sNfL levels are higher in FTLD spectrum disorder patients compared to those with PPD, which is in line with a previous report on CSF samples [12] and a recent study with serum samples [6]. As previous studies have already shown a strong correlation between serum and CSF NfL levels in various neurodegenerative disorders [13][14][15], our study emphasizes the utility of sNfL levels as a potential, minimally invasive differential diagnostic marker between FTLD and PPD.…”

Section: Discussionsupporting

confidence: 93%

“…Additionally, the heterogeneity in both FTLD and PPD groups in the cohort reflects real-life clinical practice. Compared to a recent paper with a nearly similar study approach (bvFTD vs. PPD) [6], in the present study, we have taken advantage of using a larger bvFTD cohort to confirm the findings related to the potential of sNfL as a discriminative biomarker between bvFTD and PPD. In addition, including also other clinical phenotypes of FTLD provides additional value, as prior psychiatric misdiagnoses are common also in the PPA phenotypes of FTLD [3].…”

Section: Discussionsupporting

confidence: 58%

“…The diagnostic potential of especially NfL is additionally supported by the fact that current ultrasensitive analytic platforms have enabled NfL detection from peripheral blood samples, providing a convenient and less invasive option for measuring diagnostic markers compared to CSF [5]. A recent study comprising 20 bvFTD patients and 50 psychiatric patients suggested that serum NfL (sNfL) may be used as a biomarker between bvFTD and psychiatric disorders [6].…”

Section: Introductionmentioning

confidence: 99%

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Serum neurofilament light chain is a discriminative biomarker between frontotemporal lobar degeneration and primary psychiatric disorders

et al. 2019

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Due to the significant clinical overlap between frontotemporal lobar degeneration (FTLD) spectrum disorders and lateonset primary psychiatric disorders (PPD), diagnostic biomarkers reflecting the different underlying pathophysiologies are urgently needed. Thus far, elevated cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL) have been reported in various neurological conditions. Furthermore, recent advancements in ultrasensitive analytical methods (e.g., single molecule array, Simoa) have enabled sensitive and less invasive NfL detection also from blood samples. In this study, we evaluated the potential of serum NfL (sNfL) as a diagnostic tool between FTLD and PPD. We analyzed sNfL levels with Simoa from 125 participants including patients from FTLD (n = 91) and PPD (n = 34) spectra. Our results show that sNfL levels are higher in the FTLD group compared to the PPD group as well as in separate clinical subtypes of FTLD compared to different psychiatric manifestations (i.e., mood or psychotic disorders). At single-subject level, discrimination between FTLD and PPD was possible with 80% sensitivity and 85% specificity (AUC = 0.850, 95% CI 0.776-0.923), and between behavioral variant frontotemporal dementia (bvFTD) and PPD with 79% sensitivity and 85% specificity (AUC = 0.830, 95% CI 0.732-0.908). These findings highlight the potential of sNfL as a discriminating biomarker for FTLD over PPD in patients with wide-ranging behavioral, psychiatric and cognitive symptoms.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

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Serum neurofilament light chain is a discriminative biomarker between frontotemporal lobar degeneration and primary psychiatric disorders

et al. 2019

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“…A German study assessed crosssectional differences in serum NfL levels between bvFTD and PPC (including depression, bipolar disorder, and schizophrenia). In this small-sample study, no significant changes were observed when comparing psychiatric patients with the control group, but elevated Simoa serum NfL levels (>23.7 pg/ml) in bvFTD had 85% sensitivity and 78% specificity in distinguishing of bvFTD from all psychiatric disorders as a combined group [37]. Similarly, a Finnish study comparing 91 participants with FTD and 34 with PPC, demonstrated discriminative utility of the Simoa assay with 79% sensitivity and 85% specificity (AUC = 0.830) [38].…”

Section: Discussionmentioning

confidence: 54%

Plasma Neurofilament Light: A Marker of Neurodegeneration in Mild Behavioral Impairment

Naude

Gill

et al. 2020

JAD

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Background: Assessing neuropsychiatric symptoms (NPS) in older adults is important for determining dementia risk. Mild behavioral impairment (MBI) is an at-risk state for cognitive decline and dementia, characterized by emergent NPS in later life. MBI has significantly higher dementia incidence than late life psychiatric conditions. However, its utility as a proxy for neurodegeneration has not been demonstrated. Plasma neurofilament light (NfL) is a validated biomarker of axonal damage, and has been shown to associate with hallmarks of neurodegeneration. Objective: The purpose of this investigation was to identify associations between NfL rate of change and the presence of MBI symptomatology. Methods: We evaluated the association of MBI with changes in NfL in a cohort (n = 584; MBI + n = 190, MBIn = 394) of non-demented participants from the Alzheimer's Disease Neuroimaging Initiative. MBI was determined by transforming Neuropsychiatric Inventory Questionnaire items using a published algorithm. Change in NfL was calculated over 2 years. Results: Time*MBI status was the only significant interaction to predict change in NfL concentrations (F(1,574) = 4.59, p = 0.032), even after controlling for age, mild cognitive impairment, and demographics. Analyses reclassifying 64 participants with new onset MBI over 2 years similarly demonstrated greater increases in NfL (F(1,574) = 5.82, p = 0.016).

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“…Interestingly, NfL is seemingly not elevated in Parkinson's disease (PD) in comparison to other neurodegenerative disorders and therefore a discrimination can be made from atypical parkinsonian disorders 24,25 . Furthermore, developing evidence demonstrates the potential use of using plasma NfL in discriminating FTD and primary psychiatric disorders 26,27 suggesting a potential differential diagnostic value of blood NfL in certain clinically relevant situations.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic value of plasma neurofilament light: A multicentre validation study

Ashton

Bateman

Khleifat

et al. 2020

Preprint

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Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in fifteen neurodegenerative diseases from two multicenter cohorts: King’s College London (n = 847) and the Swedish BioFINDER study (n = 1464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We further demonstrate that plasma NfL is clinically useful in identifying, i) atypical parkinsonian disorders in patients with parkinsonism, ii) dementia in individuals with Down Syndrome, iii) detect cases of frontotemporal dementia among psychiatric disorders such as moderate and severe depression, iv) identify frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related plasma NfL cut-offs for disorders with a younger age of onset. Finally, our findings suggest that plasma NfL performs best when a concentration cut-off is applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.

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Neurofilament light chain as a blood biomarker to differentiate psychiatric disorders from behavioural variant frontotemporal dementia

Cited by 91 publications

References 16 publications

Serum neurofilament light chain is a discriminative biomarker between frontotemporal lobar degeneration and primary psychiatric disorders

Serum neurofilament light chain is a discriminative biomarker between frontotemporal lobar degeneration and primary psychiatric disorders

Plasma Neurofilament Light: A Marker of Neurodegeneration in Mild Behavioral Impairment

Diagnostic value of plasma neurofilament light: A multicentre validation study

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