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- Meeter, Lieke H.H., et al.
(författare)
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Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia
- 2019
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 90:9, s. 997-1004
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Tidskriftsartikel (refereegranskat)abstract
- Background: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD. Methods: This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with clinical parameters (including survival), neuropsychological test scores and regional grey matter atrophy (including longitudinal data in a subset). Results: CSF NfL levels were significantly higher in patients with SD (median: 2326 pg/mL, IQR: 1628-3593) than in controls (577 (446-766), p<0.001). Higher CSF NfL levels were moderately associated with naming impairment as measured by the Boston Naming Test (rs=-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (rs=-0.31, p=0.004). However, cross-sectional CSF NfL levels were not associated with progression of grey matter atrophy and did not predict survival. Conclusion: CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities.
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| 2. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 3. |
- Hansson, Oskar, et al.
(författare)
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CSF placental growth factor – a novel candidate biomarker of frontotemporal dementia
- 2019
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 6:5, s. 863-872
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Diagnosis of frontotemporal dementia (FTD) is complicated by the overlap of clinical symptoms with other dementia disorders. Development of robust fluid biomarkers is critical to improve the diagnostic work-up of FTD. Methods: CSF concentrations of placental growth factor (PlGF) were measured in the discovery cohort including patients with FTD (n = 27), Alzheimer disease (AD) dementia (n = 75), DLB or PDD (n = 47), subcortical vascular dementia (VaD, n = 33), mild cognitive impairment that later converted to AD (MCI-AD, n = 34), stable MCI (sMCI, n = 62), and 50 cognitively healthy controls from the Swedish BioFINDER study. For validation, CSF PlGF was measured in additional independent cohort of FTD patients (n = 22) and controls (n = 18) from the Netherlands. Results: In the discovery cohort, MCI, MCI-AD, AD dementia, DLB-PDD, VaD, and FTD patients all showed increased CSF levels of PlGF compared with controls (sMCI P = 0.019; MCI-AD P = 0.005; AD dementia, DLB-PDD, VaD, and FTD all P < 0.001). PlGF levels were 1.8–2.1-fold higher in FTD than in AD, DLB-PDD and VaD (all P < 0.001). PlGF distinguished with high accuracy FTD from controls and sMCI performing better than tau/Aβ42 (AUC 0.954–0.996 versus 0.564–0.754, P < 0.001). A combination of PlGF, tau, and Aβ42 (tau/Aβ42/PlGF) was more accurate than tau/Aβ42 when differentiating FTD from a group of other dementias (AUC 0.972 vs. 0.932, P < 0.01). Increased CSF levels of PlGF in FTD compared with controls were corroborated in the validation cohort. Interpretation: CSF PlGF is increased in FTD compared with other dementia disorders, MCI, and healthy controls and might be useful as a diagnostic biomarker of FTD.
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