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Τρίτη 20 Νοεμβρίου 2018

Serum Neurofilament light correlates with CADASIL disease severity and survival

Abstract

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 (= 0.64, P = 0.002), brain atrophy (= −0.50, P = 0.001), and microbleed count (= 0.48, P = 0.044)], cognition [CAMCOG (= −0.45, P = 0.010), MMSE (= −0.61, P = 0.003), GIT (= −0.61, P < 0.001), TMT‐A (= 0.70, P < 0.001)) and disability (mRS (= 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.



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