Temporal alterations in cerebrospinal fluid amyloid beta-protein and apolipoprotein E after subarachnoid hemorrhage.
OBJECTIVE
The mechanism underlying the association between possession of the APOEepsilon4 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 beta-protein (Abeta), testing the hypothesis that apoE-Abeta interactions occur in vivo after SAH.


METHODS
Enzyme-linked immunosorbent assay was used to assay apoE, Abeta1-40, and Abeta1-42 in serial ventricular CSF samples from 19 patients with SAH and 13 controls. CSF S100B and tau were assayed as surrogate markers of brain injury.


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


CONCLUSIONS
After SAH both apoE and Abeta levels decrease in the CSF, supporting the concept that interactions between these proteins occur in vivo. The possibility that apoE and Abeta influence outcome after SAH warrants further investigation.
Kay
Andrew
A
Department of Neurosurgery, University of Glasgow, Institute of Neurological Sciences, Southern General Hospital, UK. adk4z@clinmed.gla.ac.uk
Petzold
Axel
A
Kerr
Mary
M
Keir
Geoff
G
Thompson
Ed
E
Nicoll
James
J
D000293:Adolescent; D000328:Adult; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001057:Apolipoproteins E / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D018450:Disease Progression; D006801:Humans; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000134:cerebrospinal fluid; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000134:cerebrospinal fluid; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid*; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins