Apolipoprotein E (ApoE) is a glycoprotein with a major role in brain lipoprotein metabolism. It has three isoforms encoded by distinct alleles: APOEε2, APOEε3 and APOEε4.

The presence of this genotype portends a worse prognosis following traumatic brain injury 1)

Furthermore, the incidence of severe traumatic brain injury in individuals with the apoE-4 allele greatly exceeds the rate of the allele in the general population 2). This allele is also a risk factor for Alzheimer’s disease 3) 4) 5) as well as for chronic traumatic encephalopathy.

Among patients with lobar hemorrhage, those with the apoE ε4 allele typically have their first hemorrhage >5 yrs earlier than noncarriers (73 ± 8 yrs vs./ 79 ± 7 yrs) 6).

Findings suggested that APOEε4 allele is a risk factor to brain function aggravation in the early stage of aneurysmal subarachnoid hemorrhage, and it may contribute to early brain injury after SAH 7).

Finding also suggests that the patients with APOEε4 allele predispose to cerebral vasospasm after spontaneous SAH 8).

The presence of APOE ε4, an elevated international normalized ratio, and a higher glucose level (≥ 10 mmol/L) are predictors of progressive traumatic intracerebral hemorrhage. Additionally, APOE ε4 is not associated with traumatic coagulopathy and patient outcome 9).

APOE ε4 and ε2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH 10).

APOEε4 may induce cerebral perfusion impairment in the early phase, contributing to early brain injury (EBI) following aneurysmal subarachnoid hemorrhage (aSAH), and assessment of APOE genotypes could serve as a useful tool in the prognostic evaluation and therapeutic management of aSAH 11).

The APOΕε4 polymorphism was analysed in 147 patients with aSAH. Allele and genotype frequencies were compared to those found in a gender- and area-matched control group of healthy individuals (n = 211). Early cerebral vasospasm (CVS) was identified and treated according to neurointensive care unit (NICU) guidelines. Neurological deficit(s) at admittance and at 1-year follow-up visit was recorded. Neurological outcome was assessed by the National Institute of Health Stroke Scale, Barthel Index and the Extended Glasgow Outcome Scale.

APOEε4 and non-APOEε4 allele frequencies were similar in aSAH patients and healthy individuals. The presence of APOEε4 was not associated with the development of early CVS. We could not find an influence of the APOE polymorphism on 1-year neurological outcome between groups. Subgroup analyses of patients treated with surgical clipping vs endovascular coiling did not reveal any associations.

The APOEε4 polymorphism has no major influence on risk of aSAH, the occurrence of CVS or long-term neurological outcome after aSAH 12).



Friedman G,Froom P,Sazbon L,et al. Apolipoprotein E-e4 Genotype Predicts a Poor Outcome in Survivors of Traumatic Injury. Neurology. 1999; 52:244– 248

Nicoll JAR, Roberts GW, Graham DI. Apolipoprotein Ee4 Allele is Associated with Deposition of Amyloid ß-Protein Following Head Injury. Nature Med. 1995; 1:135–137

Mayeux R, Ottman R, Tang MX, et al. Genetic Susceptibility and Head Injury as Risk Factors for Alz- heimer’s Disease Among Community-Dwelling Elderly Persons and Their First Degree Relatives. Ann Neurol. 1993; 33:494–501

Roberts GW, Gentleman SM, Lynch A, et al. ß Amyloid Protein Deposition in the Brain After Severe Head Injury: Implications for the Pathogenesis of Alzheimer’s Disease. J Neurol Neurosurg Psychiatry. 1994; 57:419–425

Mayeux R, Ottman R, Maestre G, et al. Synergistic Effects of Traumatic Head Injury and Apolipoprotein-e4 in Patients with Alzheimer’s Disease. Neurology. 1995; 45:555–557

Greenberg SM, Rebeck GW, Vonsattel JPV, et al. Apolipoprotein E e4 and Cerebral Hemorrhage Associated with Amyloid Angiopathy. Ann Neurol. 1995; 38:254–259

Lin B, Dan W, Jiang L, Yin XH, Wu HT, Sun XC. Association of APOE polymorphism with the change of brain function in the early stage of aneurysmal subarachnoid hemorrhage. Acta Neurochir Suppl. 2011;110(Pt 1):39-42. doi: 10.1007/978-3-7091-0353-1_7. PubMed PMID: 21116912.

Wu HT, Zhang XD, Su H, Jiang Y, Zhou S, Sun XC. Association of apolipoprotein E polymorphisms with cerebral vasospasm after spontaneous subarachnoid hemorrhage. Acta Neurochir Suppl. 2011;110(Pt 1):141-4. doi: 10.1007/978-3-7091-0353-1_24. PubMed PMID: 21116929.

Wan X, Gan C, You C, Fan T, Zhang S, Zhang H, Wang S, Shu K, Wang X, Lei T. Association of APOE ε4 with progressive hemorrhagic injury in patients with traumatic intracerebral hemorrhage. J Neurosurg. 2019 Jul 19:1-8. doi: 10.3171/2019.4.JNS183472. [Epub ahead of print] PubMed PMID: 31323634.

Marini S, Crawford K, Morotti A, Lee MJ, Pezzini A, Moomaw CJ, Flaherty ML, Montaner J, Roquer J, Jimenez-Conde J, Giralt-Steinhauer E, Elosua R, Cuadrado-Godia E, Soriano-Tarraga C, Slowik A, Jagiella JM, Pera J, Urbanik A, Pichler A, Hansen BM, McCauley JL, Tirschwell DL, Selim M, Brown DL, Silliman SL, Worrall BB, Meschia JF, Kidwell CS, Testai FD, Kittner SJ, Schmidt H, Enzinger C, Deary IJ, Rannikmae K, Samarasekera N, Salman RA, Sudlow CL, Klijn CJM, van Nieuwenhuizen KM, Fernandez-Cadenas I, Delgado P, Norrving B, Lindgren A, Goldstein JN, Viswanathan A, Greenberg SM, Falcone GJ, Biffi A, Langefeld CD, Woo D, Rosand J, Anderson CD; International Stroke Genetics Consortium. Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity: A Meta-analysis. JAMA Neurol. 2019 Feb 6. doi: 10.1001/jamaneurol.2018.4519. [Epub ahead of print] PubMed PMID: 30726504.

Cheng C, Jiang L, Yang Y, Wu H, Huang Z, Sun X. Effect of APOE Gene Polymorphism on Early Cerebral Perfusion After Aneurysmal Subarachnoid Hemorrhage. Transl Stroke Res. 2015 Sep 14. [Epub ahead of print] PubMed PMID: 26370543.

Csajbok LZ, Nylén K, Öst M, Blennow K, Zetterberg H, Nellgård P, Nellgård B. Apolipoprotein E polymorphism in aneurysmal subarachnoid haemorrhage in West Sweden. Acta Neurol Scand. 2015 Sep 16. doi: 10.1111/ane.12487. [Epub ahead of print] PubMed PMID: 26374096.

Leave a Reply