Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain

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  • Plasma C
  • Saliva C
 et al. 
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Abstract

Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer@s disease and is associated with poor clinical outcome following traumatic brain injury and other neuropathological disorders. Protein instability and an isoform-specific apoE property called domain interaction are responsible for these neuropathological effects. ApoE4 is the most neurotoxic isoform and can induce neuropathology through various cellular pathways. Neuronal damage or stress induces apoE synthesis as part of the repair response; however, when apoE4 is expressed in neurons, its unique conformation makes it susceptible to proteolysis, resulting in the generation of neurotoxic fragments. These fragments cause pathological mitochondrial dysfunction and cytoskeletal alterations. Here, we review data supporting the hypothesis that apoE4 (> apoE3 > apoE2) has direct neurotoxic effects and highlight studies showing that blocking domain interaction reverses these detrimental effects.

Author-supplied keywords

  • 1
  • 15252
  • 2
  • 2016
  • 201606210
  • 595
  • 608
  • 8
  • AD
  • ADNI
  • AGE
  • ALZHEIMER-DISEASE
  • AMERICAN
  • APOE
  • APOE GENOTYPE
  • APOLIPOPROTEIN-E
  • ASSOCIATION
  • ASSOCIATIONS
  • Abeta
  • Adolescent
  • Adult
  • Aged
  • Aging
  • Alleles
  • Alzheimer
  • Alzheimer Disease
  • Alzheimer Disease/drug therapy/genetics/ physiopat
  • Alzheimer Disease: epidemiology
  • Alzheimer Disease: genetics
  • Alzheimer Disease: metabolism
  • Alzheimer Disease: psychology
  • Alzheimer Disease: therapy
  • Alzheimer disease
  • Alzheimer's disease
  • Alzheimer’s disease
  • Amino Acid Sequence
  • Amplification refractory mutation system
  • Amyloid beta-Peptides
  • Amyloid beta-Peptides/metabolism/physiology
  • Amyloid beta-Peptides: antagonists & inhibitors
  • Amyloid beta-Peptides: genetics
  • Amyloid beta-Peptides: metabolism
  • Animals
  • ApoE
  • ApoE ε4
  • ApoE4
  • Apolipoprotein E
  • Apolipoprotein E2
  • Apolipoprotein E3
  • Apolipoprotein E4
  • Apolipoprotein E4: genetics
  • Apolipoprotein E4: metabolism
  • Apolipoproteins
  • Apolipoproteins E
  • Apolipoproteins E/drug effects/genetics/ physiolog
  • Apolipoproteins E: antagonists & inhibitors
  • Apolipoproteins E: genetics
  • Apolipoproteins E: metabolism
  • Apolipoproteins E: physiology
  • Apolipoproteins: genetics
  • BDNF
  • Binding Sites
  • Biological
  • Brain
  • Brain Injuries
  • Brain Injuries: genetics
  • Brain Injuries: physiopathology
  • Brain/drug effects/metabolism/physiopathology
  • Brain: pathology
  • COGNITIVE DECLINE
  • CORONARY HEART-DISEASE
  • Carcinoma
  • Cardiovascular Diseases
  • Cell Line
  • Cells
  • Child
  • Cholesterol
  • Cloning
  • Cognition
  • Cognition: physiology
  • Cohort Studies
  • Coronary Disease
  • Cultured
  • DIABETES-MELLITUS
  • DIFFERENCE
  • DISEASE
  • DNA
  • DNA Restriction Enzymes
  • Dementia
  • Dementia: genetics
  • Dementia: physiopathology
  • Dendritic Spines
  • Dendritic Spines: physiology
  • Diagnosis
  • Down-Regulation
  • E ALLELE EPSILON-4
  • E LOCUS
  • E POLYMORPHISM
  • EDUCATION
  • FREQUENCIES
  • FREQUENCY
  • Family Health
  • Female
  • Fibroblasts
  • Fibroblasts: metabolism
  • GENOTYPE
  • Genetic
  • Genetic Predisposition to Disease
  • Genetic Predisposition to Disease/genetics
  • Genetics
  • Genome-Wide Association Study
  • Genotype
  • HDL
  • HDL: genetics
  • HOMOZYGOTES
  • Heterozygote
  • Hippocampus atrophy
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  • Humans
  • Imaging
  • Immunofixation
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  • Isoelectric focusing
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  • Lipid Metabolism
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  • Lipid Metabolism: physiology
  • Lipids
  • Lipoproteins
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  • Low Density Lipoprotein Receptor-Related Protein-1
  • Macrophages
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  • Male
  • Mass spectrometry
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  • Memory
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  • Mutation
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  • N-Methyl-D-Aspartate
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  • Neurodegeneration
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  • Neuronal Plasticity
  • Neuronal Plasticity: genetics
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  • Nucleic Acid Hybridization
  • OLDER
  • Odds Ratio
  • PHENOTYPE
  • POPULATION
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  • Peptide Fragments
  • Peptide Fragments: metabolism
  • Peptides
  • Peptides: metabolism
  • Phenotype
  • Polymerase chain reaction
  • Predictive Value of Tests
  • Presenilins
  • Presenilins: genetics
  • Prevalence
  • Probucol
  • Protein Biosynthesis
  • Protein Interaction Mapping
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  • Single nucleotide polymorphism
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  • Statins
  • Surface Plasmon Resonance
  • Tau
  • Tetra-primer
  • Transcription
  • UTILITY
  • Vascular Diseases
  • Vascular Diseases: genetics
  • Vascular Diseases: physiopathology
  • White matter integrity
  • a b
  • accepted 10 march 2016
  • adult
  • age
  • aging
  • allele
  • alzheimer
  • alzheimer disease
  • analytic method
  • and because of a
  • apoe
  • apoe promoter polymorphisms
  • apolipoprotein
  • apolipoprotein E
  • apolipoprotein E2
  • apolipoprotein E3
  • apolipoprotein E4
  • apolipoprotein e
  • apolipoprotein e isoforms
  • apolipoprotein ε 4 allele
  • article
  • articles-original basic
  • b -amyloid
  • ber is predicted to
  • bout 44 million people
  • cardiovascular disease
  • cardiovascular risk
  • case finding
  • cell biology
  • chemistry
  • cholesterol
  • clinical
  • controlled study
  • correspondence
  • cvd
  • cvd-lipoproteins
  • demen-
  • dementia
  • diabetes
  • diagnostic panel
  • disease association
  • doi 10
  • edu
  • efficiency
  • embo mol med
  • emmm
  • epidemiology
  • family history
  • february 2016
  • female
  • frontotemporal degeneration
  • gender
  • genetic
  • genetic counseling
  • genetic polymorphism
  • genetic testing
  • genetic variability
  • genetics
  • genotype
  • genotypes
  • glucose
  • glucose intolerance
  • gumed
  • hete
  • heterogeneity
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  • human
  • human biochemical individuality
  • hypercapnia
  • hypercholesterolemia
  • inflam-
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  • lifetime risks
  • low density lipoprotein
  • major clinical study
  • male
  • mation
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  • nearly double every 20
  • neurogenetics
  • num-
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  • oral glucose
  • pl
  • population based
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  • population-based studies
  • population-based study
  • prevalence
  • prion disease
  • priority journal
  • probability
  • published online 29 march
  • rapidly aging population this
  • received 11 january 2016
  • revised 24
  • risk factor
  • s disease
  • school child
  • screening
  • tau Proteins
  • tau Proteins/metabolism/ physiology
  • tau Proteins: metabolism
  • tia
  • treatment
  • vasoreactivity
  • worldwide are living with
  • years until 2050

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Authors

  • Sample Code

  • Co Plasma

  • Co Saliva

  • Pos Con

  • Neg Con

  • Pos Con

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