Biological markers in CSF and blood for axonal degeneration in multiple sclerosis.

Biomarkers in body fluids could help to predict and monitor neurological decline in people with multiple sclerosis (MS). We discuss markers for axonal damage in body fluids in people with MS. The most promising axonal marker for discriminating patients with MS from those with other neurological diseases is the neurofilament light chain in CSF. Antibodies against the heavy-chain isoform are associated with disease progression. Other studies have shown altered CSF concentrations of tau proteins, actin, tubulin, and 14-3-3 protein. Interestingly, the concentration of 24S-hydroxycholesterol was decreased in serum of patients with MS. No clear changes have been shown for the markers apolipoprotein E and neurospecific enolase. We describe three types of markers for axonal damage: markers that reflect processes in the CNS, those that reflect extraneural processes, and those that reflect whole-body changes. These concepts may be helpful for biomarker research in various neurodegenerative diseases.

Heightened intrathecal release of axonal cytoskeletal proteins in multiple sclerosis is associated with progressive disease and clinical disability.

The pathologic basis of disease progression in multiple sclerosis (MS) is thought to involve axonal degeneration, which contributes to the accumulation of neurological disability. Recent reports suggest that intrathecal concentrations of the neurofilament protein in relapsing remitting MS correlate with disease activity and the degree of disability. We sought to investigate the intrathecal levels of other cytoskeletal components of axons, primarily actin, tubulin and the light subunit of neurofilament (NFL) in patients with progressive MS and relevant controls and correlate results with clinical parameters of disease severity. Cerebrospinal fluid (CSF) concentrations of actin, tubulin and NFL were significantly increased in MS patients when compared to corresponding levels in patients with other inflammatory or non-inflammatory neurological diseases. Moreover, the intrathecal release of actin and tubulin, and to a lesser extent NFL, was significantly more marked in patients with primary and secondary progressive MS when compared to patients with relapsing remitting disease and was correlated with clinical disability. Our findings suggest that progressive MS is associated with the heightened intrathecal release of axonal cytoskeletal proteins, and that CSF actin, tubulin and NFL are reliable markers of axonal damage.

Apolipoprotein E, transthyretin and actin in the CSF of Alzheimer's patients: relation with the senile plaques and cytoskeleton biochemistry.

We measured the levels of two beta-amyloid (Abeta)-sequestering proteins, apolipoprotein (Apo) E and transthyretin (TTR), in ventricular human cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients and controls in relation to brain histological findings. We also studied actin levels in CSF as a marker of the biochemical role of these two proteins in the cytoskeleton. We show that TTR levels in CSF were significantly decreased in AD patients compared to controls and negatively correlated with the senile plaque (SP) abundance. Moreover, actin levels were positively linked to TTR levels and increased in CSF samples of patients homozygous for the ApoE epsilon4-allele. We propose that TTR and ApoE4 may have competition in the aggregation of Abeta and its deposition in the SP of AD brain. The relationships between ApoE, TTR and actin could suggest a metabolic implication of ApoE genetics and TTR levels in cytoskeletal biochemistry which may be relevant to the pathogenesis of AD.