Brain trauma in aged transgenic mice induces regression of established Aβ deposits

Yasushi Nakagawa, Lee Reed, Michio Nakamura, Tracy K. McIntosh, Douglas H. Smith, Kathryn E. Saatman, Ramesh Raghupathi, James Clemens, Takaomi C. Saido, Virginia M.Y. Lee, John Q. Trojanowski

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


Traumatic brain injury (TBI) increases susceptibility to Alzheimer's disease (AD), but it is not known if TBI affects the progression of AD. To address this question, we studied the neuropathological consequences of TBI in transgenic (TG) mice with a mutant human Aβ precursor protein (APP) mini- gene driven by a platelet-derived (PD) growth factor promoter resulting in overexpression of mutant APP (V717F), elevated brain Aβ levels, and AD-like amyloidosis. Since brain Aβ deposits first appear in 6-month-old TG (PDAPP) mice and accumulate with age, 2-year-old PDAPP and wild-type (WT) mice were subjected to controlled cortical impact (CCI) TBI or sham treatment. At 1, 9, and 16 weeks after TBI, neuron loss, gliosis, and atrophy were most prominent near the CCI site in PDAPP and WT mice. However, there also was a remarkable regression in the Aβ amyloid plaque burden in the hippocampus ipsilateral to TBI compared to the contralateral hippocampus of the PDAPP mice by 16 weeks postinjury. Thus, these data suggest that previously accumulated Aβ plaques resulting from progressive amyloidosis in the AD brain also may be reversible. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)244-252
Number of pages9
JournalExperimental Neurology
Issue number1
StatePublished - May 2000

Bibliographical note

Funding Information:
We thank Mr. T.-H. Chiu; Ms. A. Rodoriguez; Ms. D. C. Lavalla; Ms. T. Schuck; K. M. Fung, M.D., Ph.D.; M. Grotzer, M.D.; M. L. Schmidt, Ph.D.; and J. E. Galvin, M.D., for their assistance with these studies, and Dr. Srinivasan for the caspase-3 antibody. This work was supported by grants from the National Institutes of Health (AG09215, AG11542, GM34690, NS08803, NS26818) and the Veterans Administration.


  • Alzheimer's disease
  • Amyloid plaques
  • Brain injury
  • Head trauma
  • PDAPP mice

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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