Proteomics-determined differences in the concanavalin-A-fractionated proteome of hippocampus and inferior parietal lobule in subjects with alzheimer's disease and mild cognitive impairment: Implications for progression of AD

Joshua B. Owen, Fabio Di Domenico, Rukhsana Suitana, Marzia Perluigi, Chiara Cini, William M. Pierce, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

Alzheimer's disease (AD) is the most common type of dementia, comprising 60-80% of all reported cases, and currently affects 5.2 million Americans. AD is characterized pathologically by the accumulation of senile plaques (SPs), neurofibrillary tangles (NFTs), and synapse loss. The early stages of memory loss associated with AD have been studied in a condition known as amnestic mild cognitive impairment (MCI), arguably the earliest form of AD. In spite of extensive research across a variety of disciplines, the cause of AD remains elusive. Proteomics techniques have helped to advance knowledge about AD by identifying irregularities in protein expression and post-translational modifications (PTMs) in AD brain. Glycosylation is a less studied PTM with regards to AD and MCI. This PTM is important to study because glycosylation is involved in proper protein folding, protein anchoring to cell membranes, and the delivery of proteins to organelles, and these processes are impaired in AD. Concanavalin-A (Con-A) binds to N-linked glycoproteins, but hydrophobic sites on nonglycoproteins are also known to bind Con-A. To our knowledge, the present study is the first to examine Con-A-associated brain proteins in MCI and AD with focus on the hippocampus and inferior parietal lobule (IPL) brain regions. Proteins found in AD hippocampus with altered levels are glutamate dehydrogenase (GDH), glial fibrillary acidic protein (GFAP), tropomyosin 3 (TPM3), Rab GDP-dissociation inhibitor XAP-4 (XAP4), and heat shock protein 90 (HSP90). Proteins found with altered levels in AD IPL are α-enolase, γ-enolase, and XAP-4. MCI hippocampal proteins with altered levels are dihydropyrimidase-2 (DRP2), glucose-regulated protein 78 (GRP-78), protein phosphatase related protein Sds-22 (Sds22), and GFAP and the only protein found with altered levels in MCI IPL was β-synuclein. These results are discussed with reference to biochemical and pathological alterations in and progression of AD.

Original languageEnglish
Pages (from-to)471-482
Number of pages12
JournalJournal of Proteome Research
Volume8
Issue number2
DOIs
StatePublished - Feb 2009

Keywords

  • Alzheimer's disease
  • Concanavalin -a
  • Glycoproteomics
  • Hydrophobic interactions
  • Mild cognitive impairment

ASJC Scopus subject areas

  • Biochemistry
  • General Chemistry

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