Journal article
Brain Trauma Induces Massive Hippocampal Neuron Death Linked to a Surge in β-Amyloid Levels in Mice Overexpressing Mutant Amyloid Precursor Protein
The American journal of pathology, v 153(3), pp 1005-1010
Sep 1998
PMID: 9736050
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Although brain trauma is a risk factor for Alzheimer’s disease, no experimental model has been generated to explore this relationship. We developed a model of brain trauma in transgenic mice that overexpress mutant human amyloid precursor protein (PDAPP) leading to the appearance of Alzheimer’s disease-like β-amyloid (Aβ) plaques beginning at 6 months of age. We induced cortical impact brain injury in the PDAPP animals and their wild-type littermates at 4 months of age, ie, before Aβ plaque formation, and evaluated changes in posttraumatic memory function, histopathology, and regional tissue levels of the Aβ peptides Aβ
1–40
and Aβ
1–42
. We found that noninjured PDAPP mice had impaired memory function compared to noninjured wild-type littermates (
P
< 0.01) and that brain-injured PDAPP mice had more profound memory dysfunction than brain-injured wild-type littermates (
P
< 0.001). Although no augmentation of Aβ plaque formation was observed in brain-injured PDAPP mice, a substantial exacerbation of neuron death was found in the hippocampus (
P
< 0.001) in association with an acute threefold increase in Aβ
1–40
and sevenfold increase in Aβ
1–42
levels selectively in the hippocampus (
P
< 0.01). These data suggest a mechanistic link between brain trauma and Aβ levels and the death of neurons.
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Details
- Title
- Brain Trauma Induces Massive Hippocampal Neuron Death Linked to a Surge in β-Amyloid Levels in Mice Overexpressing Mutant Amyloid Precursor Protein
- Creators
- Douglas H Smith - From the Department of Neurosurgery and the Department of Pathology and Laboratory Medicine,† University of Pennsylvania, Philadelphia, Pennsylvania; and the Lilly Research Labortories,‡ Lilly Corporate Center, Indianapolis, IndianaMichio Nakamura - From the Department of Neurosurgery and the Department of Pathology and Laboratory Medicine,† University of Pennsylvania, Philadelphia, Pennsylvania; and the Lilly Research Labortories,‡ Lilly Corporate Center, Indianapolis, IndianaTracy K McIntosh - From the Department of Neurosurgery and the Department of Pathology and Laboratory Medicine,† University of Pennsylvania, Philadelphia, Pennsylvania; and the Lilly Research Labortories,‡ Lilly Corporate Center, Indianapolis, IndianaJun Wang - From the Department of Neurosurgery and the Department of Pathology and Laboratory Medicine,† University of Pennsylvania, Philadelphia, Pennsylvania; and the Lilly Research Labortories,‡ Lilly Corporate Center, Indianapolis, IndianaAmarís Rodríguez - From the Department of Neurosurgery and the Department of Pathology and Laboratory Medicine,† University of Pennsylvania, Philadelphia, Pennsylvania; and the Lilly Research Labortories,‡ Lilly Corporate Center, Indianapolis, IndianaXiao-Han Chen - From the Department of Neurosurgery and the Department of Pathology and Laboratory Medicine,† University of Pennsylvania, Philadelphia, Pennsylvania; and the Lilly Research Labortories,‡ Lilly Corporate Center, Indianapolis, IndianaRamesh Raghupathi - From the Department of Neurosurgery and the Department of Pathology and Laboratory Medicine,† University of Pennsylvania, Philadelphia, Pennsylvania; and the Lilly Research Labortories,‡ Lilly Corporate Center, Indianapolis, IndianaKathryn E Saatman - From the Department of Neurosurgery and the Department of Pathology and Laboratory Medicine,† University of Pennsylvania, Philadelphia, Pennsylvania; and the Lilly Research Labortories,‡ Lilly Corporate Center, Indianapolis, IndianaJames Clemens - From the Department of Neurosurgery and the Department of Pathology and Laboratory Medicine,† University of Pennsylvania, Philadelphia, Pennsylvania; and the Lilly Research Labortories,‡ Lilly Corporate Center, Indianapolis, IndianaM. Luise Schmidt - From the Department of Neurosurgery and the Department of Pathology and Laboratory Medicine,† University of Pennsylvania, Philadelphia, Pennsylvania; and the Lilly Research Labortories,‡ Lilly Corporate Center, Indianapolis, IndianaVirginia M-Y Lee - From the Department of Neurosurgery and the Department of Pathology and Laboratory Medicine,† University of Pennsylvania, Philadelphia, Pennsylvania; and the Lilly Research Labortories,‡ Lilly Corporate Center, Indianapolis, IndianaJohn Q Trojanowski - From the Department of Neurosurgery and the Department of Pathology and Laboratory Medicine,† University of Pennsylvania, Philadelphia, Pennsylvania; and the Lilly Research Labortories,‡ Lilly Corporate Center, Indianapolis, Indiana
- Publication Details
- The American journal of pathology, v 153(3), pp 1005-1010
- Publisher
- American Society for Investigative Pathology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000075745500037
- Scopus ID
- 2-s2.0-0031689796
- Other Identifier
- 991014878149804721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Pathology