Quantitative Phosphoproteomic Analyses of the Inferior Parietal Lobule from Three Different Pathological Stages of Alzheimer's Disease

Judy C. Triplett, Aaron M. Swomley, Jian Cai, Jon B. Klein, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is clinically characterized by progressive neuronal loss resulting in loss of memory and dementia. AD is histopathologically characterized by the extensive distribution of senile plaques and neurofibrillary tangles, and synapse loss. Amnestic mild cognitive impairment (MCI) is generally accepted to be an early stage of AD. MCI subjects have pathology and symptoms that fall on the scale intermediately between 'normal' cognition with little or no pathology and AD. A rare number of individuals, who exhibit normal cognition on psychometric tests but whose brains show widespread postmortem AD pathology, are classified as 'asymptomatic' or 'preclinical' AD (PCAD). In this study, we evaluated changes in protein phosphorylation states in the inferior parietal lobule of subjects with AD, MCI, PCAD, and control brain using a 2-D PAGE proteomics approach in conjunction with Pro-Q Diamond phosphoprotein staining. Statistically significant changes in phosphorylation levels were found in 19 proteins involved in energy metabolism, neuronal plasticity, signal transduction, and oxidative stress response. Changes in the disease state phosphoproteome may provide insights into underlying mechanisms for the preservation of memory with expansive AD pathology in PCAD and the progressive memory loss in amnestic MCI that escalates to the dementia and the characteristic pathology of AD brain.

Original languageEnglish
Pages (from-to)45-62
Number of pages18
JournalJournal of Alzheimer's Disease
Volume49
Issue number1
DOIs
StatePublished - 2015

Bibliographical note

Publisher Copyright:
© 2016-IOS Press and the authors.

Keywords

  • Alzheimer's disease
  • amnestic mild cognitive impairment
  • neurodegeneration
  • phosphoproteomics
  • phosphorylation
  • preclinical Alzheimer's disease

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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