Abstract
The apolipoprotein E (apoE) protein is involved in clearance of β-amyloid (Aβ) from the brain; and the APOE4 gene is associated with Aβ plaque formation in humans following traumatic brain injury (TBI). Here, we examined the association between apoE and Aβ40 after experimental TBI and the effects of APOE alleles on this relationship. We report a biphasic response of soluble apoE protein after TBI with an acute reduction at 1 day postinjury followed by an increase at 7 days postinjury. TBI-induced Aβ40 levels decreased as soluble apoE levels increased. In APOE4 mice there was a diminished apoE response to TBI that corresponded to prolonged accumulation of TBI-induced Aβ40 versus that in APOE3 mice. Amyloid precursor protein processing was similar in APOE3 and APOE4 mice suggesting that impaired clearance was responsible for the abnormal accumulation of Aβ40 in the latter. Treatment of APOE4 mice with bexarotene for 7 days increased apoE4 protein levels but was not sufficient to reduce TBI-induced Aβ40 Thus, rapid clearance of TBI-induced Aβ40 occurs in mice but these pathways are impaired in APOE4 carriers. These data may help explain the deposition of Aβ in APOE4 carriers and the increased incidence of brain Aβ plaques following TBI.