To analyze whether the increase of NfL in the blood precedes leakage of the BBB indicative for the onset of acute inflammatory brain demyelination in both classical rapidly progressive CALD and smoldering CALD, we assessed NfL longitudinally in five X-ALD patients before and after the appearance of Gd-enhancing lesions on the brain MRI. The gene discussed is NEFL; the disease is adrenoleukodystrophy.