Ultrastructural studies in APP/PS1 mice expressing human apoe isoforms: Implications for Alzheimer's disease

Krikor Dikranian, Jungsu Kim, Floy R. Stewart, Marilyn A. Levy, David M. Holtzman

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)482-495
Number of pages14
JournalInternational Journal of Clinical and Experimental Pathology
Volume5
Issue number6
StatePublished - 2012
Externally publishedYes

Fingerprint

Amyloid beta-Protein Precursor
Apolipoproteins E
Alzheimer Disease
Protein Isoforms
Amyloid Plaques
Electron Microscopy
Amyloid
Brain
Presenilin-1
Neurons
Neurofibrillary Tangles
Genetically Modified Animals
Amyloidosis
Mutant Proteins
Neuroglia
Synapses
Transgenic Mice
mouse presenilin 1
Animal Models
Pathology

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • APoE
  • Electron microscopy
  • Presenilin 1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Ultrastructural studies in APP/PS1 mice expressing human apoe isoforms : Implications for Alzheimer's disease. / Dikranian, Krikor; Kim, Jungsu; Stewart, Floy R.; Levy, Marilyn A.; Holtzman, David M.

In: International Journal of Clinical and Experimental Pathology, Vol. 5, No. 6, 2012, p. 482-495.

Research output: Contribution to journalArticle

Dikranian, Krikor ; Kim, Jungsu ; Stewart, Floy R. ; Levy, Marilyn A. ; Holtzman, David M. / Ultrastructural studies in APP/PS1 mice expressing human apoe isoforms : Implications for Alzheimer's disease. In: International Journal of Clinical and Experimental Pathology. 2012 ; Vol. 5, No. 6. pp. 482-495.
@article{cf83c0e11619468181edc49724aa218d,
title = "Ultrastructural studies in APP/PS1 mice expressing human apoe isoforms: Implications for Alzheimer's disease",
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.",
keywords = "Alzheimer's disease, Amyloid precursor protein, APoE, Electron microscopy, Presenilin 1",
author = "Krikor Dikranian and Jungsu Kim and Stewart, {Floy R.} and Levy, {Marilyn A.} and Holtzman, {David M.}",
year = "2012",
language = "English (US)",
volume = "5",
pages = "482--495",
journal = "International Journal of Clinical and Experimental Pathology",
issn = "1936-2625",
publisher = "e-Century Publishing Corporation",
number = "6",

}

TY - JOUR

T1 - Ultrastructural studies in APP/PS1 mice expressing human apoe isoforms

T2 - Implications for Alzheimer's disease

AU - Dikranian, Krikor

AU - Kim, Jungsu

AU - Stewart, Floy R.

AU - Levy, Marilyn A.

AU - Holtzman, David M.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Amyloid precursor protein

KW - APoE

KW - Electron microscopy

KW - Presenilin 1

UR - http://www.scopus.com/inward/record.url?scp=84865995244&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865995244&partnerID=8YFLogxK

M3 - Article

C2 - 22949930

AN - SCOPUS:84865995244

VL - 5

SP - 482

EP - 495

JO - International Journal of Clinical and Experimental Pathology

JF - International Journal of Clinical and Experimental Pathology

SN - 1936-2625

IS - 6

ER -