| 1. |
- Götze, Karl, et al.
(författare)
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Plasma neurofilament light chain in memory clinic practice: Evidence from a real-life study.
- 2023
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Ingår i: Neurobiology of disease. - : Elsevier BV. - 1095-953X .- 0969-9961. ; 176
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Tidskriftsartikel (refereegranskat)abstract
- To explore the accuracy of plasma neurofilament light chain (NfL) as a biomarker for diagnosis and staging of cognitive impairment, in a large cohort with of previously diagnosed patients in clinical practice.Retrospective, cross-sectional, monocentric study, from a tertiary memory clinic. Patients underwent cerebrospinal fluid core Alzheimer's disease (AD) biomarker evaluation using ELISA or Elecsys methods, and plasma NfL analysis using the single molecule array technology. The patients' biomarker data were examined for associations with: i/cognitive status ii/presence of neurodegenerative disease and iii/diagnostic groups. Associations between core CSF biomarkers and plasma NfL were determined.Participants (N=558, mean age=69.2±8.8, 56.5% women) were diagnosed with AD (n=274, considering dementia and MCI stages), frontotemporal dementia (FTD, n=55), Lewy body disease (LBD, n=40, considering MCI and dementia stages), other neurodegenerative diseases, n=57 (e.g Supranuclear Palsy, Corticobasal syndrome), non-neurodegenerative cognitive impairment (NND, n=79, e.g. vascular lesions, epilepsy or psychiatric disorders) or subjective cognitive impairment (SCI, n=53). Mean plasma NfL (log, pg/mL) levels were higher in neurodegenerative than non-neurodegenerative disorders (1.35±0.2 vs 1.16±0.23, p<0.001), higher in all diagnostic groups than in SCI (1.06±0.23) p<0.001), and associated with the stage of cognitive impairment (p<0.001). The addition of plasma NfL to a clinical model (age, MMSE and APOE ε4 carriership) marginally improved the discrimination of degenerative from non-degenerative disorders in ROC analysis (AUC clinical model: 0.81, 95% CI=[0.77;0.85] AUC clinical model + plasma NfL: AUC=0.83 95% CI=[0.78;0.87], delta Akaike information criterion=-11.7).Plasma NfL could help discrimination between degenerative and non-degenerative cognitive disorders, albeit not better than comprehensive clinical evaluation.
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| 2. |
- Vrillon, Agathe, et al.
(författare)
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Comparison of CSF and plasma NfL and pNfH for Alzheimer’s disease diagnosis: a memory clinic study
- 2023
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Ingår i: Journal of Neurology. - 0340-5354 .- 1432-1459.
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Tidskriftsartikel (refereegranskat)abstract
- Plasma neurofilament light chain (NfL) is a promising biomarker of axonal damage for the diagnosis of neurodegenerative diseases. Phosphorylated neurofilament heavy chain (pNfH) has demonstrated its value in motor neuron diseases diagnosis, but has less been explored for dementia diagnosis. In a cross-sectional study, we compared cerebrospinal fluid (CSF) and plasma NfL and pNfH levels in n = 188 patients from Lariboisière Hospital, Paris, France, including AD patients at mild cognitive impairment stage (AD-MCI, n = 36) and dementia stage (n = 64), non-AD MCI (n = 38), non-AD dementia (n = 28) patients and control subjects (n = 22). Plasma NfL, plasma and CSF pNfH levels were measured using Simoa and CSF NfL using ELISA. The correlation between CSF and plasma levels was stronger for NfL than pNfH (rho = 0.77 and rho = 0.52, respectively). All neurofilament markers were increased in AD-MCI, AD dementia and non-AD dementia groups compared with controls. CSF NfL, CSF pNfH and plasma NfL showed high performance to discriminate AD at both MCI and dementia stages from control subjects [AUC (area under the curve) = 0.82–0.91]. Plasma pNfH displayed overall lower AUCs for discrimination between groups compared with CSF pNfH. Neurofilament markers showed similar moderate association with cognition. NfL levels displayed significant association with mediotemporal lobe atrophy and white matter lesions in the AD group. Our results suggest that CSF NfL and pNfH as well as plasma NfL levels display equivalent performance in both positive and differential AD diagnosis in memory clinic settings. In contrast to motoneuron disorders, plasma pNfH did not demonstrate added value as compared with plasma NfL.
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