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Journal of Neurology

Open Access 06-04-2024 | Cerebral Small Vessel Disease | Original Communication

NFL and GFAP in (pre)symptomatic RVCL-S carriers: a monogenic cerebral small vessel disease

Authors: Annelise E. Wilms, I. de Boer, N. Pelzer, S. G. J. G. in’t Veld, H. A. M. Middelkoop, C. E. Teunissen, G. M. Terwindt

Published in: Journal of Neurology

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Abstract

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

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

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*102 pg/mL vs. 3.9*102 pg/mL, p < 0.01, respectively). Serum NfL levels were higher in symptomatic RVCL-S than pre-symptomatic carriers (33.5 pg/mL vs. 5.9 pg/mL, p = 0.02). Pre-symptomatic RVCL-S carriers had increased CSF NfL levels compared to controls < 45 years (5.2*102 pg/mL vs. 1.9*102 pg/mL, p < 0.01). No differences were found in GFAP levels across groups, but in RVCL-S carriers higher serum levels of both NfL and GFAP were linked to poorer global cognitive functioning (β[95%CI] = − 2.86 [− 5.58 to − 0.13], p = 0.04 and β[95%CI] =  − 6.85 [− 11.54 to − 2.15], p = 0.01, respectively) and prolonged psychomotor test times (β[95%CI] = 6.71 [0.78–12.65], p = 0.03 and β[95%CI] = 13.84 [3.09–24.60], p = 0.01).

Discussion

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.
Literature
1.
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 3:100046PubMedPubMedCentral
2.
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):1068–1070CrossRefPubMed
3.
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):303–316CrossRefPubMed
4.
Hoogeveen ES et al (2021) Neuroimaging findings in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. AJNR Am J Neuroradiol 42(9):1604–1609CrossRefPubMedPubMedCentral
5.
6.
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):317–332CrossRefPubMed
7.
de Boer I et al (2018) RVCL-S and CADASIL display distinct impaired vascular function. Neurology 91(10):e956–e963PubMed
8.
Pelzer N et al (2017) Circulating endothelial markers in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. Stroke 48(12):3301–3307CrossRefPubMed
9.
Hoogeveen ES et al (2021) Cerebrovascular reactivity in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. J Cereb Blood Flow Metab 41(4):831–840CrossRefPubMed
10.
Teunissen CE et al (2022) Blood-based biomarkers for Alzheimer’s disease: towards clinical implementation. Lancet Neurol 21(1):66–77CrossRefPubMed
11.
van Ballegoij WJC et al (2020) Plasma NfL and GFAP as biomarkers of spinal cord degeneration in adrenoleukodystrophy. Ann Clin Transl Neurol 7(11):2127–2136CrossRefPubMedPubMedCentral
12.
Kaisey M et al (2022) An update on diagnostic laboratory biomarkers for multiple sclerosis. Curr Neurol Neurosci Rep 22(10):675–688CrossRefPubMed
13.
Khalil M et al (2018) Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol 14(10):577–589CrossRefPubMed
14.
Gaetani L et al (2019) Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry 90(8):870–881CrossRefPubMed
15.
Gravesteijn G et al (2019) Serum neurofilament light correlates with CADASIL disease severity and survival. Ann Clin Transl Neurol 6(1):46–56CrossRefPubMed
16.
17.
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):296–299CrossRefPubMedPubMedCentral
18.
Yang Z, Wang KKW (2015) Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci 38(6):364–374CrossRefPubMedPubMedCentral
19.
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):659–667CrossRef
20.
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):481–488CrossRefPubMed
21.
Abdelhak A et al (2022) Blood GFAP as an emerging biomarker in brain and spinal cord disorders. Nat Rev Neurol 18(3):158–172CrossRefPubMed
22.
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 149:698–709CrossRefPubMed
23.
Reitan RM (1955) The relation of the trail making test to organic brain damage. J Consult Psychol 19(5):393–394CrossRefPubMed
24.
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):438–450CrossRefPubMed
25.
van Swieten JC et al (1988) Interobserver agreement for the assessment of handicap in stroke patients. Stroke 19(5):604–607CrossRefPubMed
26.
Mahoney FI, Barthel DW (1965) Functional evaluation: the Barthel index. Md State Med J 14:61–65PubMed
27.
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):1655–1661CrossRefPubMed
28.
29.
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):281–298CrossRefPubMed
30.
31.
32.
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–e95CrossRefPubMed
Metadata
Title
NFL and GFAP in (pre)symptomatic RVCL-S carriers: a monogenic cerebral small vessel disease
Authors
Annelise E. Wilms
I. de Boer
N. Pelzer
S. G. J. G. in’t Veld
H. A. M. Middelkoop
C. E. Teunissen
G. M. Terwindt
Publication date
06-04-2024
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-024-12292-6