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

doi:10.1006/exnr.2000.7375

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 journal › Article › peer-review

75 Scopus citations

Abstract

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 language	English
Pages (from-to)	244-252
Number of pages	9
Journal	Experimental Neurology
Volume	163
Issue number	1
DOIs	https://doi.org/10.1006/exnr.2000.7375
State	Published - 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.

Funding

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.

Funders	Funder number
Veterans Administration
National Institutes of Health (NIH)	GM34690, NS26818, NS08803, AG11542
National Institute on Aging	P01AG009215

Keywords

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

ASJC Scopus subject areas

Neurology
Developmental Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1006/exnr.2000.7375

Cite this

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title = "Brain trauma in aged transgenic mice induces regression of established Aβ deposits",

abstract = "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.",

keywords = "Alzheimer's disease, Amyloid plaques, Brain injury, Head trauma, PDAPP mice",

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

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.",

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doi = "10.1006/exnr.2000.7375",

language = "English",

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AU - Nakagawa, Yasushi

AU - Reed, Lee

AU - Nakamura, Michio

AU - McIntosh, Tracy K.

AU - Smith, Douglas H.

AU - Saatman, Kathryn E.

AU - Raghupathi, Ramesh

AU - Clemens, James

AU - Saido, Takaomi C.

AU - Lee, Virginia M.Y.

AU - Trojanowski, John Q.

N1 - 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.

PY - 2000/5

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N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Amyloid plaques

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JO - Experimental Neurology

JF - Experimental Neurology

IS - 1

ER -

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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