One explanation is that NfL is at very low concentrations in CSF (100–500 pg/ml range).44,98,99 The levels in peripheral blood (10–100 pg/ml range) are even lower13,15 and may be masked by the high-abundance proteins in serum that make up 99% of the proteome.26,100 This is evidenced by the detection of NfL by mass spectrometry as significantly upregulated in the blood of ALS patients after depleting high-abundance proteins and enriching tissue-derived proteins101 and upregulated in CSF after using isobaric tags.102. Here, NEFL is linked to amyotrophic lateral sclerosis.