Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 46-56 |
| Number of pages | 11 |
| Journal | Annals of Clinical and Translational Neurology |
| Volume | 6 |
| Issue number | 1 |
| Early online date | 2018 |
| DOIs | |
| Publication status | Published - 1 Jan 2019 |
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Serum Neurofilament light correlates with CADASIL disease severity and survival. / Gravesteijn, Gido; Rutten, Julie W.; Verberk, Inge M. W.; Böhringer, Stefan; Liem, Michael K.; van der Grond, Jeroen; Aartsma-Rus, Annemieke; Teunissen, Charlotte E.; Lesnik Oberstein, Saskia A. J.
In: Annals of Clinical and Translational Neurology, Vol. 6, No. 1, 01.01.2019, p. 46-56.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Serum Neurofilament light correlates with CADASIL disease severity and survival
AU - Gravesteijn, Gido
AU - Rutten, Julie W.
AU - Verberk, Inge M. W.
AU - Böhringer, Stefan
AU - Liem, Michael K.
AU - van der Grond, Jeroen
AU - Aartsma-Rus, Annemieke
AU - Teunissen, Charlotte E.
AU - Lesnik Oberstein, Saskia A. J.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Objective: To validate whether serum Neurofilament Light-chain (NfL) levels correlate with disease severity in CADASIL, and to determine whether serum NfL predicts disease progression and survival. Methods: Fourty-one (pre-) manifest individuals with CADASIL causing NOTCH3 mutations and 22 healthy controls were recruited from CADASIL families. At baseline, MRI-lesion load and clinical severity was determined and serum was stored. Disease progression was measured in 30/41 patients at 7-year follow-up, and survival of all individuals was determined at 17-year follow-up. Serum NfL levels were quantified using an ultra-sensitive molecule array. Generalized estimated equation regression (GEE) was used to analyze association between serum NfL, MRI-lesion load, disease severity, and disease progression. With GEE-based Cox regression, survival was analyzed. Results: At baseline, serum NfL levels correlated with MRI-lesion load [lacune count (s = 0.64, P = 0.002), brain atrophy (r = −0.50, P = 0.001), and microbleed count (s = 0.48, P = 0.044)], cognition [CAMCOG (s = −0.45, P = 0.010), MMSE (r = −0.61, P = 0.003), GIT (r = −0.61, P < 0.001), TMT-A (r = 0.70, P < 0.001)) and disability (mRS (r = 0.70, P = 0.002)]. Baseline serum NfL predicted 7-year changes in disability (B = 0.34, P < 0.001) and cognition (CAMCOG B = −4.94, P = 0.032), as well as 17-year survival. Higher NfL levels were associated with increased mortality (HR=1.8 per twofold increase in NfL levels, P = 0.006). Interpretation: Serum NfL levels correlate with disease severity, disease progression and 17-year survival in CADASIL patients. Serum NfL is a promising biomarker to monitor and predict disease course in CADASIL, as well as potentially assessing therapeutic response in future clinical trials.
AB - Objective: To validate whether serum Neurofilament Light-chain (NfL) levels correlate with disease severity in CADASIL, and to determine whether serum NfL predicts disease progression and survival. Methods: Fourty-one (pre-) manifest individuals with CADASIL causing NOTCH3 mutations and 22 healthy controls were recruited from CADASIL families. At baseline, MRI-lesion load and clinical severity was determined and serum was stored. Disease progression was measured in 30/41 patients at 7-year follow-up, and survival of all individuals was determined at 17-year follow-up. Serum NfL levels were quantified using an ultra-sensitive molecule array. Generalized estimated equation regression (GEE) was used to analyze association between serum NfL, MRI-lesion load, disease severity, and disease progression. With GEE-based Cox regression, survival was analyzed. Results: At baseline, serum NfL levels correlated with MRI-lesion load [lacune count (s = 0.64, P = 0.002), brain atrophy (r = −0.50, P = 0.001), and microbleed count (s = 0.48, P = 0.044)], cognition [CAMCOG (s = −0.45, P = 0.010), MMSE (r = −0.61, P = 0.003), GIT (r = −0.61, P < 0.001), TMT-A (r = 0.70, P < 0.001)) and disability (mRS (r = 0.70, P = 0.002)]. Baseline serum NfL predicted 7-year changes in disability (B = 0.34, P < 0.001) and cognition (CAMCOG B = −4.94, P = 0.032), as well as 17-year survival. Higher NfL levels were associated with increased mortality (HR=1.8 per twofold increase in NfL levels, P = 0.006). Interpretation: Serum NfL levels correlate with disease severity, disease progression and 17-year survival in CADASIL patients. Serum NfL is a promising biomarker to monitor and predict disease course in CADASIL, as well as potentially assessing therapeutic response in future clinical trials.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85056796947&origin=inward
U2 - 10.1002/acn3.678
DO - 10.1002/acn3.678
M3 - Article
VL - 6
SP - 46
EP - 56
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
SN - 2328-9503
IS - 1
ER -