Tissue Transglutaminase and Its Product Isopeptide Are Increased in Alzheimer’s Disease and APPswe/PS1dE9 Double Transgenic Mice Brains

Ji Zhang, Suqing Wang, Wei Huang, David A. Bennett, Dennis W Dickson, Dengshun Wang, Rui Wang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Alzheimer’s disease (AD) is characterized by intracellular and extracellular protein aggregates, including microtubule-associated protein tau and cleavage product of amyloid precursor protein, β-amyloid (Aβ). Tissue transglutaminase (tTG) is a calcium-dependent enzyme that cross-links proteins forming a γ-glutamyl-ε-lysine isopeptide bond. Highly resistant to proteolysis, this bond can induce protein aggregation and deposition. We set out to determine if tTG may play a role in pathogenesis of AD. Previous studies have shown that tTG and isopeptide are increased in advanced AD, but they have not addressed if this is an early or late feature of AD. In the present study, we measured tTG expression levels and enzyme activity in the brains of individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD, as well as a transgenic mouse model of AD. We found that both enzyme expression and activity were increased in MCI as well as AD compared to NCI. In the transgenic model of AD, tTG expression and enzyme activity increased sharply with age and were relatively specific for the hippocampus. We also assessed overlap of isopeptide immunoreactivity with neurodegeneration-related proteins with Western blots and found neurofilament, tau, and Aβ showed co-localization with isopeptide in both AD and transgenic mice. These results suggest that tTG might be a key factor in pathogenesis of abnormal protein aggregation in AD.

Original languageEnglish (US)
JournalMolecular Neurobiology
DOIs
StateAccepted/In press - Sep 19 2015

Fingerprint

Transgenic Mice
Alzheimer Disease
Brain
Enzymes
transglutaminase 2
Proteins
Microtubule-Associated Proteins
Intermediate Filaments
Amyloid beta-Protein Precursor
Amyloid
Proteolysis
Lysine
Hippocampus
Western Blotting
Calcium
Cognitive Dysfunction

Keywords

  • Aggregate
  • Alzheimer’s disease (AD)
  • Cross-link
  • Isopeptide
  • Tissue transglutaminase (tTG)
  • γ-Glutamyl-ε-lysine

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Tissue Transglutaminase and Its Product Isopeptide Are Increased in Alzheimer’s Disease and APPswe/PS1dE9 Double Transgenic Mice Brains. / Zhang, Ji; Wang, Suqing; Huang, Wei; Bennett, David A.; Dickson, Dennis W; Wang, Dengshun; Wang, Rui.

In: Molecular Neurobiology, 19.09.2015.

Research output: Contribution to journalArticle

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