Circulating levels of neurofilament light chain as a biomarker of infarct and white matter hyperintensity volumes after ischemic stroke

• Published in: Scientific reports 2024-07, Vol.14 (1), p.16180-11, Article 16180
• Main Authors: Holmegaard, Lukas, Jensen, Christer, Pedersen, Annie, Blomstrand, Christian, Blennow, Kaj, Zetterberg, Henrik, Jood, Katarina, Jern, Christina
• Format: Article
• Language: English
• Subjects: 631/378/1689/534; 692/617/375/534; 692/617/375/599; Biomarkers; Biomarkers - blood; blood; Brain injury; Cerebral Small Vessel Diseases; Cerebral Small Vessel Diseases - blood; Cerebral Small Vessel Diseases - diagnostic imaging; Cerebral Small Vessel Diseases - pathology; diagnostic imaging; Etiology; Female; Humanities and Social Sciences; Humans; Ischemia; Ischemic Stroke; Ischemic Stroke - blood; Ischemic Stroke - diagnostic imaging; Ischemic Stroke - pathology; Magnetic Resonance Imaging; Magnetic Resonance Imaging - methods; Male; methods; Middle Aged; multidisciplinary; Neurofilament Proteins; Neurofilament Proteins - blood; Neurologi; Neurology; pathology; Science; Science (multidisciplinary); Stroke; Substantia alba; Vascular diseases; White Matter; White Matter - diagnostic imaging; White Matter - pathology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-67232-1

Serum neurofilament light chain protein (sNfL) shows promise as a biomarker for infarct size in acute ischemic stroke and for monitoring cerebral small vessel disease (cSVD). However, distinguishing the cSVD contribution after stroke may not be possible due to post-stroke sNfL increase. Additionally, it remains unclear if etiologic subtype differences exist. We measured infarct and white matter hyperintensity (WMH) volumes using MRI at the index stroke in ischemic stroke patients (n = 316, mean age 53 years, 65% males) and at 7-year follow-up (n = 187). Serum NfL concentration was measured in the acute phase (n = 235), at 3-months (n = 288), and 7-years (n = 190) post stroke. In multivariable regression, acute and 3-month sNfL concentrations were associated with infarct volume and time since stroke, but not with stroke etiology or infarct location. Seven years post-stroke, sNfL was associated with WMHs and age, but not with stroke etiology. Nonlinear regression estimated that sNfL peaks around 1 month, and declines by 50% at 3 months, and 99% at 9 months. We conclude that sNfL can indicate infarct volume and time since brain injury in the acute and subacute phases after stroke. Due to the significant post-stroke sNfL increase, several months are needed for reliable assessment of cSVD activity.