Advanced glycation end products modulate amyloidogenic APP processing and Tau phosphorylation: a mechanistic link between glycation and the development of Alzheimer’s disease

Kedar Batkulwar, Rashmi Godbole, Reema Banarjee, Omar Kassaar, Robert J Williams, Mahesh Kulkarni

Research output: Contribution to journalArticle

Abstract

Advanced glycation end products (AGEs) are implicated in the pathology of Alzheimer’s disease (AD), as they induce neurodegeneration following interaction with the receptor for AGE (RAGE). This study aimed to establish a mechanistic link between AGE-RAGE signaling and AD pathology. AGE-induced
changes in the neuro2a proteome were monitored by SWATH-MS. Western blotting and cell-based reporter assays were used to investigate AGE-RAGE regulated APP processing and tau phosphorylation in primary cortical neurons. Selected protein expression was validated in brain samples affected by AD. AGE-RAGE axis altered proteome included increased expression of Cathepsin B and asparagine endopeptidase (AEP), which mediated increase in Aβ1-42 formation and tau phosphorylation, respectively. Elevated Cathepsin B, AEP, RAGE, and pTau levels were found in human AD brain coincident with
enhanced AGEs. This study demonstrates that AGE-RAGE axis regulates Aβ1-42 formation and tau phosphorylation via increased Cathepsin B and AEP, providing a new molecular link between AGEs and AD pathology.
LanguageEnglish
Pages1-37
JournalACS Chemical Neuroscience
Early online date31 Jan 2018
DOIs
StatusE-pub ahead of print - 31 Jan 2018

Fingerprint

Advanced Glycosylation End Products
Phosphorylation
Alzheimer Disease
Endopeptidases
Cathepsin B
Asparagine
Pathology
Processing
Proteome
Brain
Neurons
Advanced Glycosylation End Product-Specific Receptor
Assays
Western Blotting
Proteins

Keywords

  • Advanced glycation end products
  • Alzheimer’s disease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Advanced glycation end products modulate amyloidogenic APP processing and Tau phosphorylation: a mechanistic link between glycation and the development of Alzheimer’s disease. / Batkulwar, Kedar; Godbole, Rashmi ; Banarjee, Reema ; Kassaar, Omar; Williams, Robert J; Kulkarni, Mahesh.

In: ACS Chemical Neuroscience, 31.01.2018, p. 1-37.

Research output: Contribution to journalArticle

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