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Int J Clin Exp Pathol 2012;5(6):482-495
Original Article
Ultrastructural studies in APP/PS1 mice expressing human ApoE isoforms: implications
for Alzheimer’s disease
Krikor Dikranian, Jungsu Kim, Floy R Stewart, Marilyn Levy, David M Holtzman
Department of Anatomy and Neurobiology, Department of Neurology, Department of 3Cell Biology and Physiology, Hope Center for
Neurological Disorders, Knight Alzheimer’s Disease Research Center, Washington University in Saint Louis, MO, USA.
Received June 27, 2012; Accepted July 23, 2012; Epub August 3, 2012; Published August 15, 2012
Abstract: Alzheimer’s disease is characterized in part by extracellular aggregation of the amyloid-β peptide in the form of diffuse and fibrillar
plaques in the brain. Electron microscopy (EM) has made an important contribution in understanding of the structure of amyloid plaques in
humans. Classical EM studies have revealed the architecture of the fibrillar core, characterized the progression of neuritic changes, and have
identified the neurofibrillary tangles formed by paired helical filaments (PHF) in degenerating neurons. Clinical data has strongly correlated
cognitive impairment in AD with the substantial synapse loss observed in these early ultrastructural studies. Animal models of AD-type brain
amyloidosis have provided excellent opportunities to study amyloid and neuritic pathology in detail and establish the role of neurons and glia in
plaque formation. Transgenic mice overexpressing mutant amyloid precursor protein (APP) alone with or without mutant presenilin 1 (PS1),
have shown that brain amyloid plaque development and structure grossly recapitulate classical findings in humans. Transgenic APP/PS1 mice
expressing human apolioprotein E isoforms also develop amyloid plaque deposition. However no ultrastructural data has been reported for
these animals. Here we show results from detailed EM analysis of amyloid plaques in APP/PS1 mice expressing human isoforms of ApoE and
compare these findings with EM data in other transgenic models and in human AD. Our results show that similar to other transgenic animals,
APP/PS1 mice expressing human ApoE isoforms share all major cellular and subcellular degenerative features and highlight the identity of the
cellular elements involved in Aβ deposition and neuronal degeneration. (IJCEP1206010)
Keywords: Alzheimer’s disease, electron microscopy, amyloid precursor protein, presenilin 1, ApoE
Address all correspondence to:
Krikor Dikranian, MD, PhD
Department of Anatomy and Neurobiology,
Washington University School of Medicine
660S. Euclid avenue, Saint Louis, MO 6311, USA
Tel: 414-362-3548
E-mail: kdikrani@pcg.wustl.edu
Original Article
Ultrastructural studies in APP/PS1 mice expressing human ApoE isoforms: implications
for Alzheimer’s disease
Krikor Dikranian, Jungsu Kim, Floy R Stewart, Marilyn Levy, David M Holtzman
Department of Anatomy and Neurobiology, Department of Neurology, Department of 3Cell Biology and Physiology, Hope Center for
Neurological Disorders, Knight Alzheimer’s Disease Research Center, Washington University in Saint Louis, MO, USA.
Received June 27, 2012; Accepted July 23, 2012; Epub August 3, 2012; Published August 15, 2012
Abstract: Alzheimer’s disease is characterized in part by extracellular aggregation of the amyloid-β peptide in the form of diffuse and fibrillar
plaques in the brain. Electron microscopy (EM) has made an important contribution in understanding of the structure of amyloid plaques in
humans. Classical EM studies have revealed the architecture of the fibrillar core, characterized the progression of neuritic changes, and have
identified the neurofibrillary tangles formed by paired helical filaments (PHF) in degenerating neurons. Clinical data has strongly correlated
cognitive impairment in AD with the substantial synapse loss observed in these early ultrastructural studies. Animal models of AD-type brain
amyloidosis have provided excellent opportunities to study amyloid and neuritic pathology in detail and establish the role of neurons and glia in
plaque formation. Transgenic mice overexpressing mutant amyloid precursor protein (APP) alone with or without mutant presenilin 1 (PS1),
have shown that brain amyloid plaque development and structure grossly recapitulate classical findings in humans. Transgenic APP/PS1 mice
expressing human apolioprotein E isoforms also develop amyloid plaque deposition. However no ultrastructural data has been reported for
these animals. Here we show results from detailed EM analysis of amyloid plaques in APP/PS1 mice expressing human isoforms of ApoE and
compare these findings with EM data in other transgenic models and in human AD. Our results show that similar to other transgenic animals,
APP/PS1 mice expressing human ApoE isoforms share all major cellular and subcellular degenerative features and highlight the identity of the
cellular elements involved in Aβ deposition and neuronal degeneration. (IJCEP1206010)
Keywords: Alzheimer’s disease, electron microscopy, amyloid precursor protein, presenilin 1, ApoE
Address all correspondence to:
Krikor Dikranian, MD, PhD
Department of Anatomy and Neurobiology,
Washington University School of Medicine
660S. Euclid avenue, Saint Louis, MO 6311, USA
Tel: 414-362-3548
E-mail: kdikrani@pcg.wustl.edu
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