Susceptibility of transgenic mice expressing human apolipoprotein E to closed head injury: The allele E3 is neuroprotective whereas E4 increases fatalities

• Published in: Neuroscience 2000-01, Vol.101 (4), p.879-884
• Main Authors: Sabo, T, Lomnitski, L, Nyska, A, Beni, S, Maronpot, R.R, Shohami, E, Roses, A.D, Michaelson, D.M
• Format: Article
• Language: English
• Subjects: Alleles; Alzheimer’s disease; animal models; Animals; apolipoprotein E3; Apolipoprotein E4; Apolipoproteins E - genetics; Biological and medical sciences; Brain - pathology; Genetic Predisposition to Disease; Head Injuries, Closed - genetics; Head Injuries, Closed - mortality; Head Injuries, Closed - pathology; Head Injuries, Closed - physiopathology; Humans; Injuries of the nervous system and the skull. Diseases due to physical agents; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic - genetics; Nervous System - physiopathology; Neuroprotective Agents - metabolism; Reference Values; Traumas. Diseases due to physical agents; traumatic brain injury
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(00)00438-3

Apolipoprotein E, the major brain lipid-binding protein, is expressed in humans as three common isoforms (E2, E3 and E4). Previous studies revealed that the allele apolipoprotein E4 is a major genetic risk factor of Alzheimer’s disease and that traumatic brain injury is associated with increased risk for developing this disease. Furthermore, it has been suggested that the effects of traumatic head injury and apolipoprotein E4 in Alzheimer’s disease are synergistic. To test the hypothesis that the apolipoprotein E genotype affects susceptibility to brain injury, we subjected transgenic mice, expressing either human apolipoprotein E3 or human apolipoprotein E4 on a null mouse apolipoprotein E background and apolipoprotein E-deficient knockouts, to closed head injury and compared mortality, neurological recovery and the extent of brain damage of the survivors. More than 50% of the transgenic mice expressing human apolipoprotein E4 died following closed head injury, whereas only half as many of the transgenic mice expressing human apolipoprotein E3, and of the control and apolipoprotein E-deficient mice died during this period ( P