apolipoprotein e2


Summary: One of three major isoforms of apolipoprotein E. In humans, Apo E2 differs from APOLIPOPROTEIN E3 at one residue 158 where arginine is replaced by cysteine (R158--C). In contrast to Apo E3, Apo E2 displays extremely low binding affinity for LDL receptors (RECEPTORS, LDL) which mediate the internalization and catabolism of lipoprotein particles in liver cells. ApoE2 allelic homozygosity is associated with HYPERLIPOPROTEINEMIA TYPE III.

Top Publications

  1. Nicoll J, Burnett C, Love S, Graham D, Dewar D, Ironside J, et al. High frequency of apolipoprotein E epsilon 2 allele in hemorrhage due to cerebral amyloid angiopathy. Ann Neurol. 1997;41:716-21 pubmed
    ..We conclude that whereas possession of apoE epsilon 2 may be a risk factor for cerebral hemorrhage due to CAA, apoE epsilon 4 is a risk factor for concomitant AD but not an independent risk factor for CAA-related hemorrhage. ..
  2. McCarron M, Nicoll J, Stewart J, Ironside J, Mann D, Love S, et al. The apolipoprotein E epsilon2 allele and the pathological features in cerebral amyloid angiopathy-related hemorrhage. J Neuropathol Exp Neurol. 1999;58:711-8 pubmed
    ..Fibrinoid necrosis alone was associated with the APOE epsilon2 allele (p < 0.04) and we suggest that over-representation of APOE epsilon2 in CAAH may result from its association with fibrinoid necrosis. ..
  3. Daniele A, Matera M, Seripa D, Acciarri A, Bizzarro A, Pilotto A, et al. APOE epsilon 2/epsilon 4 genotype a risk factor for primary progressive aphasia in women. Arch Neurol. 2009;66:910-2 pubmed publisher
  4. Payami H, Zareparsi S, Montee K, Sexton G, Kaye J, Bird T, et al. Gender difference in apolipoprotein E-associated risk for familial Alzheimer disease: a possible clue to the higher incidence of Alzheimer disease in women. Am J Hum Genet. 1996;58:803-11 pubmed
    ..These observations are consistent with the increased incidence of familial AD in women and may be a critical clue to the role of gender in the pathogenesis of AD. ..
  5. Miyata M, Smith J. Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nat Genet. 1996;14:55-61 pubmed
    ..E2 > E3 > E4 possessed antioxidant activity, and apoE bound certain metal ions. The decreased antioxidant activity of E4 could contribute to its association with Alzheimer's disease, cardiovascular disease and decreased longevity. ..
  6. Yang D, Smith J, Zhou Z, Gandy S, Martins R. Characterization of the binding of amyloid-beta peptide to cell culture-derived native apolipoprotein E2, E3, and E4 isoforms and to isoforms from human plasma. J Neurochem. 1997;68:721-5 pubmed
    ..The different A beta-binding properties of native apoE4 versus native apoE3 provide insight into the molecular mechanisms by which the APOE epsilon 4 allele exerts its risk factor effects in AD. ..
  7. Greenberg S, Vonsattel J, Segal A, Chiu R, Clatworthy A, Liao A, et al. Association of apolipoprotein E epsilon2 and vasculopathy in cerebral amyloid angiopathy. Neurology. 1998;50:961-5 pubmed
  8. Ma J, Yee A, Brewer H, Das S, Potter H. Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments. Nature. 1994;372:92-4 pubmed
    ..These and other experiments suggest that Alzheimer amyloid deposits arise when A beta is induced to form filaments by amyloid-promoting factors (pathological chaperones) expressed in certain brain regions. ..
  9. Blazejewska Hyzorek B, Gromadzka G, Skowronska M, Czlonkowska A. APOE ? 2 allele is an independent risk factor for vulnerable carotid plaque in ischemic stroke patients. Neurol Res. 2014;36:950-4 pubmed publisher
    ..3 for <60% stenosis and OR ?=? 2.7 for ?60% stenosis; 95% CI). This study suggests that ? 2 allele is an independent risk factor for echolucent and ulcerated carotid plaque. ..

More Information


  1. Pankiewicz J, Guridi M, Kim J, Asuni A, Sanchez S, Sullivan P, et al. Blocking the apoE/A? interaction ameliorates A?-related pathology in APOE ?2 and ?4 targeted replacement Alzheimer model mice. Acta Neuropathol Commun. 2014;2:75 pubmed publisher
    ..These results indicate that both apoE2 and apoE4 isoforms contribute to A? deposition and future therapies targeting the apoE/A? interaction could produce favorable outcome in APOE ?2 and ?4 allele carriers. ..
  2. Lim Y, Mormino E. APOE genotype and early ?-amyloid accumulation in older adults without dementia. Neurology. 2017;89:1028-1034 pubmed publisher
    ..i>APOE genotype in conjunction with chronologic age may aid in participant selection for primary prevention trials aimed at halting A? accumulation before abnormal levels are reached. ..
  3. Liu M, Li Y, Han L, Zhang Y, Wang D, Wang Z, et al. Adipose-derived stem cells were impaired in restricting CD4+T cell proliferation and polarization in type 2 diabetic ApoE-/- mouse. Mol Immunol. 2017;87:152-160 pubmed publisher
    ..T2DM ADSCs had impaired function in restricting CD4+T lymphocyte proliferation and pro-inflammatory polarization due to immune phenotypic changes. ..
  4. Yamauchi K, Ebihara Y, Kawakami Y. Redox status of serum apolipoprotein E and its impact on HDL cholesterol levels. Clin Biochem. 2017;50:777-783 pubmed publisher
    ..001). The redox status of serum apoE might be related to the synthesis of HDL. The information concerning the redox status of serum apoE provided by the present method may be a potent indicator to evaluate various apoE-related diseases. ..
  5. Gesierich B, Opherk C, Rosand J, Gonik M, Malik R, Jouvent E, et al. APOE ɛ2 is associated with white matter hyperintensity volume in CADASIL. J Cereb Blood Flow Metab. 2016;36:199-203 pubmed
    ..02) but not APOE ɛ4. The results remained significant when controlled for genome-wide genetic background variation. Our findings suggest a modifying influence of APOE ɛ2 on WMHV caused by pure SVD. ..
  6. Saito T, Matsunaga A. Significance of a novel apolipoprotein E variant, ApoE Osaka/Kurashiki, in lipoprotein glomerulopathy. J Atheroscler Thromb. 2011;18:542-3 pubmed
  7. Messier C, Gagnon M. Cognitive decline associated with dementia and type 2 diabetes: the interplay of risk factors. Diabetologia. 2009;52:2471-4 pubmed publisher
  8. Wozniak M, Maude R, Innes J, Hawkey P, Itzhaki R. Apolipoprotein E-epsilon2 confers risk of pulmonary tuberculosis in women from the Indian subcontinent--a preliminary study. J Infect. 2009;59:219-22 pubmed publisher
  9. Federoff H. Alzheimer's disease: reducing the burden with ApoE2. Gene Ther. 2005;12:1019-29 pubmed