Neurofilament protein in cerebrospinal fluid: A marker of white matter changes

The objective of this study was to compare cerebrospinal fluid (CSF) levels of the light subtype of the neurofilament proteins (NFL), tau, and beta -a myioid42 (A beta 42) in individuals with moderate or severe white matter ch anges (WMC) and in those with mild or no WMC. Twenty-two patients with Alzh eimer's disease (AD), nine patients with subcortical vascular dementia (SVD ), and 20 normal controls were included in the study. The occurrence of WMC was evaluated by a neuroradiologist using the Blennow-Wallin scale. Thirty -seven subjects had no or only punctate WMC 14 had moderate to severe WMC. Both diagnostic group and WMC, but not gender or apolipoproteinE E4 inherit ance, contributed to the variance in the CSF levels of tau, NFL, and A beta 42. In patients with moderate to severe WMC, CSF NFL (P < 0.01), but not C SF tau or CSF A beta 42, was increased also after correction for age, gende r, and degree of cognitive impairment. A comparison between patients and co ntrols with any signs of WIVIC and those without such signs yielded a simil ar result: CSF NFL (P < 0.001) was increased in the group with signs of WMC . As in numerous previous studies, we found that CSF tau was increased in A D (P < 0.001) compared with controls. Furthermore, CSF NFL was increased in both AD and SVD compared with controls (P < 0.001 for both). Although diag nostic group seems to be a stronger predictor of the variance found in CSF NFL, a clear association between the presence of WIVIC and increased CSF NF L was found. Because NFL is located mainly in large myelinated axons, incre ased CSF NFL in individuals with WMC probably reflects axonal degeneration. (C) 2001 Wiley-Liss, Inc.