Published Online
on November 6, 2003

A more recent version of this article appeared on December 1, 2003

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Submitted on June 19, 2003
Accepted on July 30, 2003

Temporal Alterations in Cerebrospinal Fluid Amyloid -Protein and Apolipoprotein E After Subarachnoid Hemorrhage

Andrew Kay MBBS^*; Axel Petzold PhD; Mary Kerr PhD; Geoff Keir PhD; Ed Thompson DSc; and James Nicoll MD

From the Department of Neurosurgery, University of Glasgow, Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK (A.K.); Department of Neuroimmunology, University of London, Institute of Neurology and Neurosurgery, London, UK (A.P., G.K., E.T.); Department of Neurosurgery and Center for Nursing Research, University of Pittsburgh, Pittsburgh, Pa (M.K.); and Division of Clinical Neurosciences, University of Southampton, Southampton General Hospital, Southampton, UK (J.N.).

^* To whom correspondence should be addressed. E-mail: adk4z{at}clinmed.gla.ac.uk.

Background and Purpose--The mechanism underlying the association between possession of the APOE4 allele and less favorable outcome after subarachnoid hemorrhage (SAH) remains to be determined. After SAH the level of apolipoprotein E (apoE) in the cerebrospinal fluid (CSF) is decreased, and lower levels are associated with more severe injury and less favorable outcome. This study examined serial CSF samples to determine the time course for the decrease in CSF apoE and the relationship between CSF apoE and amyloid -protein (A), testing the hypothesis that apoE-A interactions occur in vivo after SAH.

Methods--Enzyme-linked immunosorbent assay was used to assay apoE, A_1-40, and A_1-42 in serial ventricular CSF samples from 19 patients with SAH and 13 controls. CSF S100B and were assayed as surrogate markers of brain injury.

Results--There was a sustained decrease in CSF apoE (P<0.001) and A (P<0.001) after SAH in contrast to the observed elevation in CSF S100B (P<0.001) and (P<0.001) concentration. There was significant correlation between CSF A concentration and clinical outcome (r=0.65, P<0.01), and the decrease in CSF A concentration correlated significantly with that of apoE (r=0.85, P<0.0001).

Conclusions--After SAH both apoE and A levels decrease in the CSF, supporting the concept that interactions between these proteins occur in vivo. The possibility that apoE and A influence outcome after SAH warrants further investigation.

Key words: amyloid • apolipoprotein • cerebrospinal fluid • subarachnoid hemorrhage

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