Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease

Roger M. Lane, Martin Farlow

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Extracellular amyloid plaques, intracellular neurofibrillary tangles, and loss of basal forebrain cholinergic neurons in the brains of Alzheimer's disease (AD) patients may be the end result of abnormalities in lipid metabolism and peroxidation that may be caused, or exacerbated, by β-amyloid peptide (Aβ). Apolipoprotein E (apoE) is a major apolipoprotein in the brain, mediating the transport and clearance of lipids and Aβ. ApoE-dependent dendritic and synaptic regeneration may be less efficient with apoE4, and this may result in, or unmask, age-related neurodegenerative changes. The increased risk of AD associated with apoE4 may be modulated by diet, vascular risk factors, and genetic polymorphisms that affect the function of other transporter proteins and enzymes involved in brain lipid homeostasis. Diet and apoE lipoproteins influence membrane lipid raft composition and the properties of enzymes, transporter proteins, and receptors mediating Aβ production and degradation, tau phosphorylation, glutamate and glucose uptake, and neuronal signal transduction. The level and isoform of apoE may influence whether Aβ is likely to be metabolized or deposited. This review examines the current evidence for diet, lipid homeostasis, and apoE in the pathogenesis of AD. Effects on the cholinergic system and response to cholinesterase inhibitors by APOE allele carrier status are discussed briefly.

Original languageEnglish
Pages (from-to)949-968
Number of pages20
JournalJournal of Lipid Research
Volume46
Issue number5
DOIs
StatePublished - 2005

Fingerprint

Apolipoproteins E
Alzheimer Disease
Homeostasis
Lipids
Nutrition
Apolipoprotein E4
Brain
Diet
Amyloid
Cholinergic Agents
Lipid A
Signal transduction
Neurofibrillary Tangles
Phosphorylation
Cholinergic Neurons
Apolipoproteins
Cholinesterase Inhibitors
Amyloid Plaques
Brain Diseases
Genetic Polymorphisms

Keywords

  • Carbohydrate
  • Cholesterol
  • Lipid raft
  • Long-chain polyunsaturated essential fatty acid

ASJC Scopus subject areas

  • Endocrinology

Cite this

Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease. / Lane, Roger M.; Farlow, Martin.

In: Journal of Lipid Research, Vol. 46, No. 5, 2005, p. 949-968.

Research output: Contribution to journalArticle

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