Plasmalogen deficiency in early Alzheimer's disease subjects and in animal models: Molecular characterization using electrospray ionization mass spectrometry

Xianlin Han, David M. Holtzman, Daniel W. McKeel

Research output: Contribution to journalArticle

304 Scopus citations

Abstract

To explore the hypothesis that alterations in ethanolamine plasmalogen may be directly related to the severity of dementia in Alzheimer's disease (AD), we performed a systematic examination of plasmalogen content in cellular membranes of gray and white matter from different regions of human subjects with a spectrum of AD clinical dementia ratings (CDR) using electrospray ionization mass spectrometry (ESI/MS). The results demonstrate: (1) a dramatic decrease in plasmalogen content (up to 40 mol% of total plasmalogen) in white matter at a very early stage of AD (i.e. CDR 0.5); (2) a correlation of the deficiency in gray matter plasmalogen content with the AD CDR (i.e. ∼10 mol% of deficiency at CDR 0.5 (very mild dementia) to ∼30 mol% of deficiency at CDR 3 (severe dementia); (3) an absence of alterations of plasmalogen content and molecular species in cerebellar gray matter at any CDR despite dramatic alterations of plasmalogen content in cerebellar white matter. Alterations of ethanolamine plasmalogen content in two mouse models of AD, APPV717F and APPsw, were also examined by ESI/MS. A plasmalogen deficiency was present (up to 10 mol% of total plasmalogen at the age of 18 months) in cerebral cortices, but was absent in cerebella from both animal models. These results suggest plasmalogen deficiency may play an important role in the AD pathogenesis, particularly in the white matter, and suggest that altered plasmalogen content may contribute to neurodegeneration, synapse loss and synaptic dysfunction in AD.

Original languageEnglish (US)
Pages (from-to)1168-1180
Number of pages13
JournalJournal of neurochemistry
Volume77
Issue number4
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Electrospray ionization
  • Lipid peroxidation
  • Mass spectrometry
  • Oxidative stress
  • Plasmalogen deficiency

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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