Anomalies occurring in lipid profiles and protein distribution in frontal cortex lipid rafts in dementia with Lewy bodies disclose neurochemical traits partially shared by Alzheimer's and Parkinson's diseases

Neurobiol Aging. 2017 Jan:49:52-59. doi: 10.1016/j.neurobiolaging.2016.08.027. Epub 2016 Sep 6.

Abstract

Lipid rafts are highly dynamic membrane microdomains intimately associated with cell signaling. Compelling evidence has demonstrated that alterations in lipid rafts are associated with neurodegenerative diseases such Alzheimer's disease, but at present, whether alterations in lipid raft microdomains occur in other types of dementia such dementia with Lewy bodies (DLB) remains unknown. Our analyses reveal that lipid rafts from DLB exhibit aberrant lipid profiles including low levels of n-3 long-chain polyunsaturated fatty acids (mainly docosahexaenoic acid), plasmalogens and cholesterol, and reduced unsaturation and peroxidability indexes. As a consequence, lipid raft resident proteins holding principal factors of the β-amyloidogenic pathway, including β-amyloid precursor protein, presenilin 1, β-secretase, and PrP, are redistributed between lipid rafts and nonraft domains in DLB frontal cortex. Meta-analysis discloses certain similarities in the altered composition of lipid rafts between DLB and Parkinson's disease which are in line with the spectrum of Lewy body diseases. In addition, redistribution of proteins linked to the β-amyloidogenic pathway in DLB can facilitate generation of β-amyloid, thus providing mechanistic clues to the intriguing convergence of Alzheimer's disease pathology, particularly β-amyloid deposition, in DLB.

Keywords: Alzheimer's disease; Amyloid precursor protein; Amyloidogenic processing; Cholesterol; Docosahexaenoic acid; Human brain cortex; Lewy body diseases; Lipid rafts; Parkinson's disease; Plasmalogens; β-secretase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism*
  • Amyloid Precursor Protein Secretases / metabolism
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / metabolism
  • Cholesterol / metabolism
  • Docosahexaenoic Acids / metabolism
  • Female
  • Frontal Lobe / cytology*
  • Frontal Lobe / metabolism*
  • Humans
  • Lewy Body Disease / metabolism*
  • Lipid Metabolism*
  • Male
  • Membrane Microdomains / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Parkinson Disease / metabolism*
  • Plasmalogens / metabolism

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Nerve Tissue Proteins
  • Plasmalogens
  • Docosahexaenoic Acids
  • Cholesterol
  • Amyloid Precursor Protein Secretases