NFL and GFAP in (pre)symptomatic RVCL-S carriers: a monogenic cerebral small vessel disease.
Cerebral small vessel disease (SVD)
Glial fibrillary acidic protein (GFAP)
Neurofilament light chain (NfL)
Neuroinflammation
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S)
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
06 Apr 2024
06 Apr 2024
Historique:
received:
10
01
2024
accepted:
29
02
2024
revised:
28
02
2024
medline:
6
4
2024
pubmed:
6
4
2024
entrez:
6
4
2024
Statut:
aheadofprint
Résumé
Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have emerged as biomarkers for cerebral small vessel disease (SVD). We investigated their role in a hereditary SVD model, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S). NfL and GFAP levels of 17 pre-symptomatic, 22 symptomatic RVCL-S mutation carriers and 69 controls were measured using a Simoa assay. We assessed the association of serum and cerebrospinal fluid (CSF) levels of NfL and GFAP with RVCL-S symptomatology and neuropsychological functioning. Serum and CSF NfL levels were higher in symptomatic RVCL-S compared to controls ≥ 45 years (33.5 pg/mL vs. 9.2 pg/mL, p < 0.01; 8.5*10 Higher levels of serum NfL and GFAP are associated with worse cognitive functioning in RVCL-S carriers and may serve as marker for disease progression. CSF NfL levels may serve as early marker as pre-symptomatic RVCL-S patients already show differences compared to young controls.
Sections du résumé
BACKGROUND
BACKGROUND
Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have emerged as biomarkers for cerebral small vessel disease (SVD). We investigated their role in a hereditary SVD model, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S).
METHODS
METHODS
NfL and GFAP levels of 17 pre-symptomatic, 22 symptomatic RVCL-S mutation carriers and 69 controls were measured using a Simoa assay. We assessed the association of serum and cerebrospinal fluid (CSF) levels of NfL and GFAP with RVCL-S symptomatology and neuropsychological functioning.
RESULTS
RESULTS
Serum and CSF NfL levels were higher in symptomatic RVCL-S compared to controls ≥ 45 years (33.5 pg/mL vs. 9.2 pg/mL, p < 0.01; 8.5*10
DISCUSSION
CONCLUSIONS
Higher levels of serum NfL and GFAP are associated with worse cognitive functioning in RVCL-S carriers and may serve as marker for disease progression. CSF NfL levels may serve as early marker as pre-symptomatic RVCL-S patients already show differences compared to young controls.
Identifiants
pubmed: 38581544
doi: 10.1007/s00415-024-12292-6
pii: 10.1007/s00415-024-12292-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Stichting Dioraphte
ID : 20010407
Organisme : Hartstichting
ID : 2020T065
Organisme : European Community
ID : 101070917
Informations de copyright
© 2024. The Author(s).
Références
Wilms AE, de Boer I, Terwindt GM (2022) Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S): an update on basic science and clinical perspectives. Cereb Circ Cogn Behav 3:100046
pubmed: 36324396
pmcid: 9616387
Richards A et al (2007) C-terminal truncations in human 3’-5’ DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nat Genet 39(9):1068–1070
doi: 10.1038/ng2082
pubmed: 17660820
Terwindt GM et al (1998) Clinical and genetic analysis of a large Dutch family with autosomal dominant vascular retinopathy, migraine and Raynaud’s phenomenon. Brain 121(2):303–316
doi: 10.1093/brain/121.2.303
pubmed: 9549508
Hoogeveen ES et al (2021) Neuroimaging findings in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. AJNR Am J Neuroradiol 42(9):1604–1609
doi: 10.3174/ajnr.A7194
pubmed: 34167956
pmcid: 8423035
Stam AH et al (2016) Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. Brain 139(11):2909–2922
doi: 10.1093/brain/aww217
pubmed: 27604306
pmcid: 5091044
Pelzer N et al (2019) Systemic features of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a monogenic small vessel disease. J Intern Med 285(3):317–332
doi: 10.1111/joim.12848
pubmed: 30411414
de Boer I et al (2018) RVCL-S and CADASIL display distinct impaired vascular function. Neurology 91(10):e956–e963
pubmed: 30076273
Pelzer N et al (2017) Circulating endothelial markers in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. Stroke 48(12):3301–3307
doi: 10.1161/STROKEAHA.117.018556
pubmed: 29114091
Hoogeveen ES et al (2021) Cerebrovascular reactivity in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. J Cereb Blood Flow Metab 41(4):831–840
doi: 10.1177/0271678X20929430
pubmed: 33736510
Teunissen CE et al (2022) Blood-based biomarkers for Alzheimer’s disease: towards clinical implementation. Lancet Neurol 21(1):66–77
doi: 10.1016/S1474-4422(21)00361-6
pubmed: 34838239
van Ballegoij WJC et al (2020) Plasma NfL and GFAP as biomarkers of spinal cord degeneration in adrenoleukodystrophy. Ann Clin Transl Neurol 7(11):2127–2136
doi: 10.1002/acn3.51188
pubmed: 33047897
pmcid: 7664277
Kaisey M et al (2022) An update on diagnostic laboratory biomarkers for multiple sclerosis. Curr Neurol Neurosci Rep 22(10):675–688
doi: 10.1007/s11910-022-01227-1
pubmed: 36269540
Khalil M et al (2018) Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol 14(10):577–589
doi: 10.1038/s41582-018-0058-z
pubmed: 30171200
Gaetani L et al (2019) Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry 90(8):870–881
doi: 10.1136/jnnp-2018-320106
pubmed: 30967444
Gravesteijn G et al (2019) Serum neurofilament light correlates with CADASIL disease severity and survival. Ann Clin Transl Neurol 6(1):46–56
doi: 10.1002/acn3.678
pubmed: 30656183
Duering M et al (2018) Serum neurofilament light chain levels are related to small vessel disease burden. J Stroke 20(2):228–238
doi: 10.5853/jos.2017.02565
pubmed: 29886723
pmcid: 6007291
Jacob MA et al (2022) Increased neurofilament light chain is associated with increased risk of long-term mortality in cerebral small vessel disease. J Stroke 24(2):296–299
doi: 10.5853/jos.2021.04385
pubmed: 35677985
pmcid: 9194543
Yang Z, Wang KKW (2015) Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci 38(6):364–374
doi: 10.1016/j.tins.2015.04.003
pubmed: 25975510
pmcid: 4559283
Oeckl P et al (2022) Serum GFAP differentiates Alzheimer’s disease from frontotemporal dementia and predicts MCI-to-dementia conversion. J Neurol Neurosurg Psychiatry 93(6):659–667
doi: 10.1136/jnnp-2021-328547
Oeckl P et al (2019) Glial fibrillary acidic protein in serum is increased in Alzheimer’s disease and correlates with cognitive impairment. J Alzheimers Dis 67(2):481–488
doi: 10.3233/JAD-180325
pubmed: 30594925
Abdelhak A et al (2022) Blood GFAP as an emerging biomarker in brain and spinal cord disorders. Nat Rev Neurol 18(3):158–172
doi: 10.1038/s41582-021-00616-3
pubmed: 35115728
Roth M et al (1986) CAMDEX. A standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. Br J Psychiatry 149:698–709
doi: 10.1192/bjp.149.6.698
pubmed: 3790869
Reitan RM (1955) The relation of the trail making test to organic brain damage. J Consult Psychol 19(5):393–394
doi: 10.1037/h0044509
pubmed: 13263471
Sánchez-Cubillo I et al (2009) Construct validity of the Trail Making Test: role of task-switching, working memory, inhibition/interference control, and visuomotor abilities. J Int Neuropsychol Soc 15(3):438–450
doi: 10.1017/S1355617709090626
pubmed: 19402930
van Swieten JC et al (1988) Interobserver agreement for the assessment of handicap in stroke patients. Stroke 19(5):604–607
doi: 10.1161/01.STR.19.5.604
pubmed: 3363593
Mahoney FI, Barthel DW (1965) Functional evaluation: the Barthel index. Md State Med J 14:61–65
pubmed: 14258950
Kuhle J et al (2016) Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa. Clin Chem Lab Med 54(10):1655–1661
doi: 10.1515/cclm-2015-1195
pubmed: 27071153
Gafson AR et al (2020) Neurofilaments: neurobiological foundations for biomarker applications. Brain 143(7):1975–1998
doi: 10.1093/brain/awaa098
pubmed: 32408345
pmcid: 7363489
Garwood CJ et al (2017) Review: astrocytes in Alzheimer’s disease and other age-associated dementias: a supporting player with a central role. Neuropathol Appl Neurobiol 43(4):281–298
doi: 10.1111/nan.12338
pubmed: 27442752
Huss A et al (2022) Association of serum GFAP with functional and neurocognitive outcome in sporadic small vessel disease. Biomedicines 10(8):1869
doi: 10.3390/biomedicines10081869
pubmed: 36009416
pmcid: 9405121
Gattringer T et al (2017) Serum neurofilament light is sensitive to active cerebral small vessel disease. Neurology 89(20):2108–2114
doi: 10.1212/WNL.0000000000004645
pubmed: 29046363
pmcid: 5711505
Verberk IMW et al (2021) Serum markers glial fibrillary acidic protein and neurofilament light for prognosis and monitoring in cognitively normal older people: a prospective memory clinic-based cohort study. Lancet Healthy Longev 2(2):e87–e95
doi: 10.1016/S2666-7568(20)30061-1
pubmed: 36098162