Lipidomic analysis of brain tissues and plasma in a mouse model expressing mutated human amyloid precursor protein/tau for Alzheimer's disease

Yoko Tajima, Masaki Ishikawa, Keiko Maekawa, Mayumi Murayama, Yuya Senoo, Tomoko Nishimaki-Mogami, Hiroki Nakanishi, Kazutaka Ikeda, Makoto Arita, Ryo Taguchi, Alato Okuno, Ryuta Mikawa, Shumpei Niida, Osamu Takikawa, Yoshiro Saito

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Background: Alzheimer's disease (AD), the most common cause of dementia among neurodegenerative diseases, afflicts millions of elderly people worldwide. In addition to amyloid-beta (Aβ) peptide and phosphorylated tau, lipid dysregulation is suggested to participate in AD pathogenesis. However, alterations in individual lipid species and their role in AD disease progression remain unclear. Methods. We performed a lipidomic analysis using brain tissues and plasma obtained from mice expressing mutated human amyloid precursor protein (APP) and tau protein (Tg2576×JNPL3) (APP/tau mice) at 4 (pre-symptomatic phase), 10 (early symptomatic) and 15 months (late symptomatic). Results: Levels of docosahexaenoyl (22:6) cholesterol ester (ChE) were markedly increased in APP/tau mice compared to controls at all stages examined. Several species of ethanolamine plasmalogens (pPEs) and sphingomyelins (SMs) showed different levels between brains from APP/tau and control mice at various stages of AD. Increased levels of 12-hydroxyeicosatetraenoic acid (12-HETE) during the early symptomatic phase were consistent with previous reports using human AD brain tissue. In addition, 19,20-dihydroxy-docosapentaenoic acid (19,20-diHDoPE) and 17,18-dihydroxy-eicosatetraenoic acid (17,18-diHETE), which are produced from docosahexaenoic acid and eicosapentaenoic acid via 19,20-epoxy-docosapentaenoic acid (19,20-EpDPE) and 17,18-epoxy-eicosatetraenoic acid (17,18-EpETE), respectively, were significantly increased in APP/tau brains during the pre-symptomatic phase, and concomitant increases occurred in plasma. Several arachidonic acid metabolites such as prostaglandin D2 (PGD 2) and 15-hydroxyeicosatetraenoic acid (15-HETE), which have potential deteriorating and protective actions, respectively, were decreased in the early symptomatic phase of APP/tau mice. Significant decreases in phosphatidylcholines and PEs with polyunsaturated fatty acids were also detected in the late symptomatic phase, indicating a perturbation of membrane properties. Conclusion: Our results provide fundamental information on lipid dysregulation during various stages of human AD.

Original languageEnglish
Article number68
JournalLipids in Health and Disease
Volume12
Issue number1
DOIs
Publication statusPublished - 2013
Externally publishedYes

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Amyloid beta-Protein Precursor
Brain
Alzheimer Disease
Tissue
Plasmas
Arachidonic Acids
Hydroxyeicosatetraenoic Acids
Lipids
Prostaglandin D2
tau Proteins
Neurodegenerative diseases
Eicosapentaenoic Acid
Sphingomyelins
Docosahexaenoic Acids
Cholesterol Esters
Amyloid beta-Peptides
Phosphatidylcholines
Unsaturated Fatty Acids
Arachidonic Acid
Neurodegenerative Diseases

Keywords

  • Alzheimer's disease
  • Ethanolamine plasmalogens
  • Lipidomic analysis
  • Mice model
  • Oxidative fatty acids

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Lipidomic analysis of brain tissues and plasma in a mouse model expressing mutated human amyloid precursor protein/tau for Alzheimer's disease. / Tajima, Yoko; Ishikawa, Masaki; Maekawa, Keiko; Murayama, Mayumi; Senoo, Yuya; Nishimaki-Mogami, Tomoko; Nakanishi, Hiroki; Ikeda, Kazutaka; Arita, Makoto; Taguchi, Ryo; Okuno, Alato; Mikawa, Ryuta; Niida, Shumpei; Takikawa, Osamu; Saito, Yoshiro.

In: Lipids in Health and Disease, Vol. 12, No. 1, 68, 2013.

Research output: Contribution to journalArticle

Tajima, Y, Ishikawa, M, Maekawa, K, Murayama, M, Senoo, Y, Nishimaki-Mogami, T, Nakanishi, H, Ikeda, K, Arita, M, Taguchi, R, Okuno, A, Mikawa, R, Niida, S, Takikawa, O & Saito, Y 2013, 'Lipidomic analysis of brain tissues and plasma in a mouse model expressing mutated human amyloid precursor protein/tau for Alzheimer's disease', Lipids in Health and Disease, vol. 12, no. 1, 68. https://doi.org/10.1186/1476-511X-12-68
Tajima, Yoko ; Ishikawa, Masaki ; Maekawa, Keiko ; Murayama, Mayumi ; Senoo, Yuya ; Nishimaki-Mogami, Tomoko ; Nakanishi, Hiroki ; Ikeda, Kazutaka ; Arita, Makoto ; Taguchi, Ryo ; Okuno, Alato ; Mikawa, Ryuta ; Niida, Shumpei ; Takikawa, Osamu ; Saito, Yoshiro. / Lipidomic analysis of brain tissues and plasma in a mouse model expressing mutated human amyloid precursor protein/tau for Alzheimer's disease. In: Lipids in Health and Disease. 2013 ; Vol. 12, No. 1.
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T1 - Lipidomic analysis of brain tissues and plasma in a mouse model expressing mutated human amyloid precursor protein/tau for Alzheimer's disease

AU - Tajima, Yoko

AU - Ishikawa, Masaki

AU - Maekawa, Keiko

AU - Murayama, Mayumi

AU - Senoo, Yuya

AU - Nishimaki-Mogami, Tomoko

AU - Nakanishi, Hiroki

AU - Ikeda, Kazutaka

AU - Arita, Makoto

AU - Taguchi, Ryo

AU - Okuno, Alato

AU - Mikawa, Ryuta

AU - Niida, Shumpei

AU - Takikawa, Osamu

AU - Saito, Yoshiro

PY - 2013

Y1 - 2013

N2 - Background: Alzheimer's disease (AD), the most common cause of dementia among neurodegenerative diseases, afflicts millions of elderly people worldwide. In addition to amyloid-beta (Aβ) peptide and phosphorylated tau, lipid dysregulation is suggested to participate in AD pathogenesis. However, alterations in individual lipid species and their role in AD disease progression remain unclear. Methods. We performed a lipidomic analysis using brain tissues and plasma obtained from mice expressing mutated human amyloid precursor protein (APP) and tau protein (Tg2576×JNPL3) (APP/tau mice) at 4 (pre-symptomatic phase), 10 (early symptomatic) and 15 months (late symptomatic). Results: Levels of docosahexaenoyl (22:6) cholesterol ester (ChE) were markedly increased in APP/tau mice compared to controls at all stages examined. Several species of ethanolamine plasmalogens (pPEs) and sphingomyelins (SMs) showed different levels between brains from APP/tau and control mice at various stages of AD. Increased levels of 12-hydroxyeicosatetraenoic acid (12-HETE) during the early symptomatic phase were consistent with previous reports using human AD brain tissue. In addition, 19,20-dihydroxy-docosapentaenoic acid (19,20-diHDoPE) and 17,18-dihydroxy-eicosatetraenoic acid (17,18-diHETE), which are produced from docosahexaenoic acid and eicosapentaenoic acid via 19,20-epoxy-docosapentaenoic acid (19,20-EpDPE) and 17,18-epoxy-eicosatetraenoic acid (17,18-EpETE), respectively, were significantly increased in APP/tau brains during the pre-symptomatic phase, and concomitant increases occurred in plasma. Several arachidonic acid metabolites such as prostaglandin D2 (PGD 2) and 15-hydroxyeicosatetraenoic acid (15-HETE), which have potential deteriorating and protective actions, respectively, were decreased in the early symptomatic phase of APP/tau mice. Significant decreases in phosphatidylcholines and PEs with polyunsaturated fatty acids were also detected in the late symptomatic phase, indicating a perturbation of membrane properties. Conclusion: Our results provide fundamental information on lipid dysregulation during various stages of human AD.

AB - Background: Alzheimer's disease (AD), the most common cause of dementia among neurodegenerative diseases, afflicts millions of elderly people worldwide. In addition to amyloid-beta (Aβ) peptide and phosphorylated tau, lipid dysregulation is suggested to participate in AD pathogenesis. However, alterations in individual lipid species and their role in AD disease progression remain unclear. Methods. We performed a lipidomic analysis using brain tissues and plasma obtained from mice expressing mutated human amyloid precursor protein (APP) and tau protein (Tg2576×JNPL3) (APP/tau mice) at 4 (pre-symptomatic phase), 10 (early symptomatic) and 15 months (late symptomatic). Results: Levels of docosahexaenoyl (22:6) cholesterol ester (ChE) were markedly increased in APP/tau mice compared to controls at all stages examined. Several species of ethanolamine plasmalogens (pPEs) and sphingomyelins (SMs) showed different levels between brains from APP/tau and control mice at various stages of AD. Increased levels of 12-hydroxyeicosatetraenoic acid (12-HETE) during the early symptomatic phase were consistent with previous reports using human AD brain tissue. In addition, 19,20-dihydroxy-docosapentaenoic acid (19,20-diHDoPE) and 17,18-dihydroxy-eicosatetraenoic acid (17,18-diHETE), which are produced from docosahexaenoic acid and eicosapentaenoic acid via 19,20-epoxy-docosapentaenoic acid (19,20-EpDPE) and 17,18-epoxy-eicosatetraenoic acid (17,18-EpETE), respectively, were significantly increased in APP/tau brains during the pre-symptomatic phase, and concomitant increases occurred in plasma. Several arachidonic acid metabolites such as prostaglandin D2 (PGD 2) and 15-hydroxyeicosatetraenoic acid (15-HETE), which have potential deteriorating and protective actions, respectively, were decreased in the early symptomatic phase of APP/tau mice. Significant decreases in phosphatidylcholines and PEs with polyunsaturated fatty acids were also detected in the late symptomatic phase, indicating a perturbation of membrane properties. Conclusion: Our results provide fundamental information on lipid dysregulation during various stages of human AD.

KW - Alzheimer's disease

KW - Ethanolamine plasmalogens

KW - Lipidomic analysis

KW - Mice model

KW - Oxidative fatty acids

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