Significance of Apolipoprotein E in Subarachnoid Hemorrhage: Neuronal Injury, Repair, and Therapeutic Perspectives–A Review

Subarachnoid hemorrhage (SAH) strikes individuals at a young age with devastating neurologic consequences. Classic formulations that correlate complications and outcome with clinical variables do not explain all the heterogeneity that is usually found in clinical practice. The role of genetic predisposition has recently been investigated. Particular attention has been paid to the apolipoprotein E (APOE) genotype that encodes for a polymorphic protein existing as 3 isoforms (apoE2, apoE3, apoE4), products of alleles E2, E3, and E4 at a single gene locus. ApoE is produced by astrocytes and exerts complex neuroprotective functions that make it a hub of the biochemical network of SAH. The neuroprotective effectiveness of the apoE4 isoform is reduced with respect to the others and this has made the E4 allele a risk factor candidate. Recently published observational studies and meta-analyses suggested that the APOE genotype may strongly improve the usual predictive model with the possibility of optimizing clinical decisions according to the individual's needs. Furthermore, the clinical results, together with new biological insights, suggest that SAH may be a possible candidate for the ongoing research on apoE-based neuroprotective therapy. This article reviews the clinical studies, analyzes their methodology, and surveys the biological links between the physiopathology of SAH and apoE and the possible prospects.