Tau in serum and CSF during cerebral injury

Introduction

Elevated levels of neuron-specific proteins, such as neuron-specific enolase (NSE) and/or neuromodulin in serum or cerebrospinal fluid (CSF) of brain trauma patients are of prognostic value for the patients' outcome. Recently tau, a neuron-specific microtubule-associated protein, has been found to be elevated in CSF of Alzheimer patients. This elevation is at least partially due to loss of neuronal cells. Until now tau has not been detected in serum. Therefore, we investigated whether tau in serum or CSF can be used as a marker for neuronal loss in patients with various forms of acute cerebral injury.

Materials and methods

Consecutive samples of CSF and serum of patients admitted to the intensive care unit with cerebrospinal drain were simultaneously drawn on a daily basis. Tau was determined by Innotest hTau antigen (Innogenetics, Gent, Belgium).

Results

Forty-four CSF and serum samples were evaluated from eight patients suffering craniocerebral trauma (n = 4, GCS < 8, 2 survivals), tumor surgery complicated with massive edema (n = 1, survived), subarachnoidal hemorrhage (SAH, n = 1, GCS < 6, survived) and intracerebral hemorrhage (n = 1, died). In CSF, tau was correlated (r²= 0.406, P < 0.01) with neuromodulin. In CSF, the lowest maximal tau values were found in the patient with SAH (628 pg/ml) well above the normal levels 150–200 pg/ml found in control patients. The other patients had very high tau concentrations (maximal values > 10,000 pg/ml). No correlation was found between tau and total protein concentrations or the serum/CSF albumin quotient. In this preliminary study we found no correlation with survival, severity of the disease or outcome. Tau was found to be increased in the serum in all trauma patients (182 to 1200 pg/ml), but not in the others.

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Conclusion

Tau is increased in CSF after severe cerebral injury indicating the occurrence of recent neuronal damage. A further increase of tau in CSF after admission implies a secondary neuronal damage. Craniocerebral trauma, accompanied by damage to the blood-brain barrier, results in detection of tau in serum.