Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. 2012

David M Holtzman, and Joachim Herz, and Guojun Bu
Department of Neurology, Alzheimer's Disease Research Center, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri 63110, USA. holtzman@neuro.wustl.edu

Apolipoprotein E (APOE) genotype is the major genetic risk factor for Alzheimer disease (AD); the ε4 allele increases risk and the ε2 allele is protective. In the central nervous system (CNS), apoE is produced by glial cells, is present in high-density-like lipoproteins, interacts with several receptors that are members of the low-density lipoprotein receptor (LDLR) family, and is a protein that binds to the amyloid-β (Aβ) peptide. There are a variety of mechanisms by which apoE isoform may influence risk for AD. There is substantial evidence that differential effects of apoE isoform on AD risk are influenced by the ability of apoE to affect Aβ aggregation and clearance in the brain. Other mechanisms are also likely to play a role in the ability of apoE to influence CNS function as well as AD, including effects on synaptic plasticity, cell signaling, lipid transport and metabolism, and neuroinflammation. ApoE receptors, including LDLRs, Apoer2, very low-density lipoprotein receptors (VLDLRs), and lipoprotein receptor-related protein 1 (LRP1) appear to influence both the CNS effects of apoE as well as Aβ metabolism and toxicity. Therapeutic strategies based on apoE and apoE receptors may include influencing apoE/Aβ interactions, apoE structure, apoE lipidation, LDLR receptor family member function, and signaling. Understanding the normal and disease-related biology connecting apoE, apoE receptors, and AD is likely to provide novel insights into AD pathogenesis and treatment.

UI MeSH Term Description Entries
D009473 Neuronal Plasticity The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations. Brain Plasticity,Plasticity, Neuronal,Axon Pruning,Axonal Pruning,Dendrite Arborization,Dendrite Pruning,Dendritic Arborization,Dendritic Pruning,Dendritic Remodeling,Neural Plasticity,Neurite Pruning,Neuronal Arborization,Neuronal Network Remodeling,Neuronal Pruning,Neuronal Remodeling,Neuroplasticity,Synaptic Plasticity,Synaptic Pruning,Arborization, Dendrite,Arborization, Dendritic,Arborization, Neuronal,Arborizations, Dendrite,Arborizations, Dendritic,Arborizations, Neuronal,Axon Prunings,Axonal Prunings,Brain Plasticities,Dendrite Arborizations,Dendrite Prunings,Dendritic Arborizations,Dendritic Prunings,Dendritic Remodelings,Network Remodeling, Neuronal,Network Remodelings, Neuronal,Neural Plasticities,Neurite Prunings,Neuronal Arborizations,Neuronal Network Remodelings,Neuronal Plasticities,Neuronal Prunings,Neuronal Remodelings,Neuroplasticities,Plasticities, Brain,Plasticities, Neural,Plasticities, Neuronal,Plasticities, Synaptic,Plasticity, Brain,Plasticity, Neural,Plasticity, Synaptic,Pruning, Axon,Pruning, Axonal,Pruning, Dendrite,Pruning, Dendritic,Pruning, Neurite,Pruning, Neuronal,Pruning, Synaptic,Prunings, Axon,Prunings, Axonal,Prunings, Dendrite,Prunings, Dendritic,Prunings, Neurite,Prunings, Neuronal,Prunings, Synaptic,Remodeling, Dendritic,Remodeling, Neuronal,Remodeling, Neuronal Network,Remodelings, Dendritic,Remodelings, Neuronal,Remodelings, Neuronal Network,Synaptic Plasticities,Synaptic Prunings
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000544 Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57) Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001057 Apolipoproteins E A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III. Apo-E,Apo E,Apo E Isoproteins,ApoE,Apolipoprotein E Isoproteins,Apoprotein (E),Apoproteins E,Isoproteins, Apo E,Isoproteins, Apolipoprotein E
D016229 Amyloid beta-Peptides Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue. Alzheimer beta-Protein,Amyloid Protein A4,Amyloid beta-Peptide,Amyloid beta-Protein,beta Amyloid,beta-Amyloid Protein,Alzheimer's ABP,Alzheimer's Amyloid Fibril Protein,Amyloid AD-AP,Amyloid Fibril Protein, Alzheimer's,Amyloid beta-Proteins,ABP, Alzheimer's,AD-AP, Amyloid,Alzheimer ABP,Alzheimer beta Protein,Alzheimers ABP,Amyloid AD AP,Amyloid beta Peptide,Amyloid beta Peptides,Amyloid beta Protein,Amyloid beta Proteins,Amyloid, beta,Protein A4, Amyloid,Protein, beta-Amyloid,beta Amyloid Protein,beta-Peptide, Amyloid,beta-Peptides, Amyloid,beta-Protein, Alzheimer,beta-Protein, Amyloid,beta-Proteins, Amyloid
D053327 Apolipoprotein E4 A major and the second most common isoform of apolipoprotein E. In humans, Apo E4 differs from APOLIPOPROTEIN E3 at only one residue 112 (cysteine is replaced by arginine), and exhibits a lower resistance to denaturation and greater propensity to form folded intermediates. Apo E4 is a risk factor for ALZHEIMER DISEASE and CARDIOVASCULAR DISEASES. Apo E epsilon 4,Apo E-4,Apo E4,ApoE4,Apolipoprotein E-4,Apo E 4,Apolipoprotein E 4

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