RT Journal Article
SR Electronic
T1 Repetitive Mild Brain Trauma Accelerates Aβ Deposition, Lipid Peroxidation, and Cognitive Impairment in a Transgenic Mouse Model of Alzheimer Amyloidosis
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 446
OP 454
DO 10.1523/JNEUROSCI.22-02-00446.2002
VO 22
IS 2
A1 Kunihiro Uryu
A1 Helmut Laurer
A1 Tracy McIntosh
A1 Domenico Praticò
A1 Daniel Martinez
A1 Susan Leight
A1 Virginia M.-Y. Lee
A1 John Q. Trojanowski
YR 2002
UL http://www.jneurosci.org/content/22/2/446.abstract
AB Traumatic brain injury (TBI) increases susceptibility to Alzheimer's disease (AD), but it is not known how TBI contributes to the onset or progression of this common late life dementia. To address this question, we studied neuropathological and behavioral consequences of single versus repetitive mild TBI (mTBI) in transgenic (Tg) mice (Tg2576) that express mutant human Aβ precursor protein, and we demonstrate elevated brain Aβ levels and increased Aβ deposition. Nine-month-old Tg2576 and wild-type mice were subjected to single (n = 15) or repetitive (n = 39) mTBI or sham treatment (n = 37). At 2 d and 9 and 16 weeks after treatment, we assessed brain Aβ deposits and levels in addition to brain and urine isoprostanes generated by lipid peroxidation in these mice. A subset of mice also was studied behaviorally at 16 weeks after injury. Repetitive but not single mTBI increased Aβ deposition as well as levels of Aβ and isoprostanes only in Tg mice, and repetitive mTBI alone induced cognitive impairments but no motor deficits in these mice. This is the first experimental evidence linking TBI to mechanisms of AD by showing that repetitive TBI accelerates brain Aβ accumulation and oxidative stress, which we suggest could work synergistically to promote the onset or drive the progression of AD. Additional insights into the role of TBI in mechanisms of AD pathobiology could lead to strategies for reducing the risk of AD associated with previous episodes of brain trauma and for preventing progressive brain amyloidosis in AD patients.