The role of lipids and membranes in the pathogenesis of alzheimer's disease: A comprehensive view

Botond Penke, Gábor Paragi, János Gera, Róbert Berkecz, Zsolt Kovács, Tim Crul, László Vígh

Research output: Contribution to journalReview article

16 Citations (Scopus)

Abstract

Lipids participate in Amyloid Precursor Protein (APP) trafficking and processing-important factors in the initiation of Alzheimer’s disease (AD) pathogenesis and influence the formation of neurotoxic β-amyloid (Aβ) peptides. An important risk factor, the presence of ApoE4 protein in AD brain cells binds the lipids to AD. In addition, lipid signaling pathways have a crucial role in the cellular homeostasis and depend on specific protein-lipid interactions. The current review focuses on pathological alterations of membrane lipids (cholesterol, glycerophospholipids, sphingolipids) and lipid metabolism in AD and provides insight in the current understanding of biological membranes, their lipid structures and functions, as well as their role as potential therapeutic targets. Novel methods for studying the membrane structure and lipid composition will be reviewed in a broad sense whereas the use of lipid biomarkers for early diagnosis of AD will be shortly summarized. Interactions of Aβ peptides with the cell membrane and different subcellular organelles are reviewed. Next, the details of the most important lipid signaling pathways, including the role of the plasma membrane as stress sensor and its therapeutic applications are given. 4-hydroxy-2-nonenal may play a special role in the initiation of the pathogenesis of AD and thus the “calpain-cathepsin hypothesis” of AD is highlighted. Finally, the most important lipid dietary factors and their possible use and efficacy in the prevention of AD are discussed.

Original languageEnglish
Pages (from-to)1191-1212
Number of pages22
JournalCurrent Alzheimer Research
Volume15
Issue number13
DOIs
Publication statusPublished - Jan 1 2018

Keywords

  • 4-hydroxy-2-nonenal
  • Alzheimer’s disease
  • Apoe
  • Lipid dietary factors
  • Lipid-protein interactions
  • Lipids
  • Lipids in aβ aggregation
  • Membrane lipid therapy
  • Membranes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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