Protein Biomarkers for Amyotrophic Lateral Sclerosis

Henrik Ryberg, PhD; Robert Bowser, PhD†

Expert Rev Proteomics. 2008;5(2):249-262.

Disease Progression Biomarkers

The ultimate goal for much ALS research is to find therapeutic interventions that can slow or reverse disease progression. In order to evaluate such interventions, disease progression biomarkers or surrogate markers would be extremely valuable tools. Unfortunately, very little has been done in the field of ALS disease progression biomarkers. There is a notable lack of longitudinal studies, which is probably a consequence of the rapid disease progression.

However, a number of recent studies have reported potential disease progression biomarkers. In a large study, the survival time for 403 ALS patients correlated to apolipoprotein E (APOE) phenotype and APOE plasma levels.^[94] The plasma levels of APOE were not determined for the controls. However, approximately one quarter of the ALS patients had levels above the maximum reference level and for those patients the disease progression rate was significantly more rapid. This study suggests that APOE could be a progression biomarker for ALS, but further longitudinal studies that correlate the levels to clinical measures are needed.

In another study, EPO levels were measured in the serum and CSF from 60 ALS patients.^[49] These patients were further stratified as either slowly progressing (n = 30) or rapidly progressing (n = 30). The investigators demonstrated that CSF EPO levels in the rapidly progressing group were approximately half of those in the slowly progressing group. The levels in serum were similar for the two groups. These data suggest that EPO might also be a useful progression biomarker, but further studies are needed to correlate EPO levels to clinical measures such as the ALS functional rating scale or forced vital capacity.

A recent study reported a negative correlation between disease progression and CSF levels of NFL in 78 ALS patients.^[85] ALS patients with NFL levels over the median had considerably shorter disease duration. A similar relationship has also been shown for neurofilament heavy protein in the CSF from 20 ALS patients.^[84] This same study also followed changes for CSF tau longitudinally in a smaller number of patients. In another study serum collagen IV protein was found to be slightly elevated in ALS patients with disease duration longer than 3 years (n = 19) as compared with patients with shorter duration (n = 11).^[70] This longitudinal study also followed changes for CSF tau in a smaller number of patients. Furthermore, it has been reported that TGFβ1 levels in plasma showed a correlation to disease duration, although this study only included 11 ALS patients^[65] and in another study CSF levels of VEGF in 30 ALS patients were correlated to disease duration.^[78]

Additional studies are needed to find definitive biomarkers that function as surrogate markers of disease progression in ALS, as well as to validate already published potential disease progression biomarkers. Longitudinal studies that correlate the surrogate marker to clinical measures would be especially valuable.

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Cite this: Protein Biomarkers for Amyotrophic Lateral Sclerosis - Medscape - Apr 01, 2008.

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