Role of A β Transport and Clearance in the Pathogenesis and Treatment of Alzheimer’s Disease

The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics

2002 • 13,092 citations

Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families

1993 • 8,888 citations

Alzheimer's Disease: Genes, Proteins, and Therapy

2001 • 5,919 citations

Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.

1993 • 4,145 citations

Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology

1988 • 3,984 citations

Secreted amyloid β–protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease

1996 • 2,543 citations

RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease

1996 • 1,955 citations

Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease

1994 • 1,813 citations

RAGE Mediates a Novel Proinflammatory Axis

1999 • 1,807 citations

Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production

1992 • 1,723 citations

Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.

1993 • 1,480 citations

Familial Alzheimer's Disease–Linked Presenilin 1 Variants Elevate Aβ1–42/1–40 Ratio In Vitro and In Vivo

1996 • 1,467 citations

An Increased Percentage of Long Amyloid β Protein Secreted by Familial Amyloid β Protein Precursor (βApp ₇₁₇ ) Mutants

1994 • 1,463 citations

Insulin-degrading enzyme regulates the levels of insulin, amyloid β-protein, and the β-amyloid precursor protein intracellular domain in vivo

2003 • 1,393 citations

Mutation of the Alzheimer's Disease Amyloid Gene in Hereditary Cerebral Hemorrhage, Dutch Type

1990 • 1,361 citations

Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease.

1993 • 1,329 citations

Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor–related protein-1 at the blood-brain barrier

2000 • 1,296 citations

RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain

2003 • 1,289 citations

Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease

2001 • 1,264 citations

Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease

1991 • 1,133 citations

The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Aβ protofibril formation

2001 • 1,126 citations

The Receptor for Advanced Glycation End Products (RAGE) Is a Cellular Binding Site for Amphoterin

1995 • 1,116 citations

Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions

1993 • 1,092 citations

Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease

2001 • 990 citations

LRP: a multifunctional scavenger and signaling receptor

2001 • 975 citations

Metabolic Regulation of Brain Aβ by Neprilysin

2001 • 918 citations

Release of Excess Amyloid β Protein from a Mutant Amyloid β Protein Precursor

1993 • 909 citations

Neurovascular mechanisms of Alzheimer's neurodegeneration

2005 • 903 citations

Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease

2000 • 896 citations

Amyloid-associated proteins α1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments

1994 • 866 citations

LRP: a multifunctional scavenger and signaling receptor

2001 • 856 citations

Adult mouse astrocytes degrade amyloid-β in vitro and in situ

2003 • 850 citations

N ε-(Carboxymethyl)Lysine Adducts of Proteins Are Ligands for Receptor for Advanced Glycation End Products That Activate Cell Signaling Pathways and Modulate Gene Expression

1999 • 848 citations

Apolipoprotein E: A pathological chaperone protein in patients with cerebral and systemic amyloid

1992 • 802 citations

Differential Effects of Apolipoproteins E3 and E4 on Neuronal Growth in Vitro

1994 • 797 citations

Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system.

1985 • 786 citations

LRP/Amyloid β-Peptide Interaction Mediates Differential Brain Efflux of Aβ Isoforms

2004 • 769 citations

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.

1987 • 696 citations

Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins

1987 • 666 citations

Cerebral Amyloid Angiopathy

1998 • 654 citations

Apolipoprotein E in animal models of CNS injury and in alzheimer's disease

1994 • 651 citations

P-glycoprotein deficiency at the blood-brain barrier increases amyloid- deposition in an Alzheimer disease mouse model

2005 • 609 citations

Plasma and Cerebrospinal Fluid Levels of Amyloid β Proteins 1-40 and 1-42 in Alzheimer Disease

2000 • 564 citations

Brain to Plasma Amyloid-β Efflux: a Measure of Brain Amyloid Burden in a Mouse Model of Alzheimer's Disease

2002 • 557 citations

Targeted Replacement of the Mouse Apolipoprotein E Gene with the Common Human APOE3 Allele Enhances Diet-induced Hypercholesterolemia and Atherosclerosis

1997 • 545 citations

Clearing the Brain's Amyloid Cobwebs

2001 • 538 citations

Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides

2004 • 530 citations

Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis

2002 • 527 citations

Apolipoprotein E ϵ4 and cerebral hemorrhage associated with amyloid angiopathy

1995 • 525 citations

Apolipoprotein E is essential for amyloid deposition in the APP ^V717F transgenic mouse model of Alzheimer's disease

1999 • 467 citations

Apolipoprotein E and Alzheimer's Disease

1996 • 457 citations

Serum insulin-like growth factor I regulates brain amyloid-β levels

2002 • 440 citations

Plasma Aβ40 and Aβ42 and Alzheimer’s disease

2003 • 425 citations

In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life.

2003 • 422 citations

ApoE and Clusterin Cooperatively Suppress Aβ Levels and Deposition

2004 • 421 citations

Glycoprotein 330/megalin: probable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer disease amyloid beta at the blood-brain and blood-cerebrospinal fluid barriers.

1996 • 414 citations

Involvement of Microglial Receptor for Advanced Glycation Endproducts (RAGE) in Alzheimer's Disease: Identification of a Cellular Activation Mechanism

2001 • 412 citations

Clearance of Alzheimer's Aβ Peptide

2004 • 411 citations

Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3.

1994 • 407 citations

The apolipoprotein ε4 allele in patients with Alzheimer's disease

1993 • 401 citations

Human Apolipoprotein E Receptor 2

1996 • 378 citations

RAGE (Yin) Versus LRP (Yang) Balance Regulates Alzheimer Amyloid β-Peptide Clearance Through Transport Across the Blood–Brain Barrier

2004 • 377 citations

Linkage of Plasma Aβ42 to a Quantitative Locus on Chromosome 10 in Late-Onset Alzheimer's Disease Pedigrees

2000 • 375 citations

β‐Amyloid efflux mediated by p‐glycoprotein

2001 • 368 citations

In VivoAssessment of Brain Interstitial Fluid with Microdialysis Reveals Plaque-Associated Changes in Amyloid-β Metabolism and Half-Life

2003 • 363 citations

Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line.

1995 • 355 citations

Expression of human apolipoprotein E reduces amyloid-β deposition in a mouse model of Alzheimer's disease

1999 • 342 citations

Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease.

1996 • 340 citations

Expression of human apolipoprotein E3 or E4 in the brains of Apoe-/- mice: isoform-specific effects on neurodegeneration.

1999 • 340 citations

Early-onset and Robust Cerebral Microvascular Accumulation of Amyloid β-Protein in Transgenic Mice Expressing Low Levels of a Vasculotropic Dutch/Iowa Mutant Form of Amyloid β-Protein Precursor

2004 • 338 citations

Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation.

1991 • 334 citations

Apolipoprotein E is a kinetic but not a thermodynamic inhibitor of amyloid formation: implications for the pathogenesis and treatment of Alzheimer disease.

1995 • 332 citations

Clearing amyloid through the blood–brain barrier

2004 • 326 citations

Clusterin promotes amyloid plaque formation and is critical for neuritic toxicity in a mouse model of Alzheimer's disease

2002 • 325 citations

Novel Therapeutic Approach for the Treatment of Alzheimer's Disease by Peripheral Administration of Agents with an Affinity to β-Amyloid

2003 • 322 citations

Plastic Neuronal Remodeling Is Impaired in Patients with Alzheimer’s Disease Carrying Apolipoprotein ε4 Allele

1997 • 321 citations

Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer's disease model

2000 • 307 citations

A polymorphism in the regulatory region of APOE associated with risk for Alzheimer's dementia

1998 • 287 citations

Expression of Human Apolipoprotein E3 or E4 in the Brains ofApoe^−/−Mice: Isoform-Specific Effects on Neurodegeneration

1999 • 283 citations

Biochemical detection of Aβ isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimer’s disease

2000 • 282 citations

Nascent Astrocyte Particles Differ from Lipoproteins in CSF

1998 • 281 citations

Receptor for advanced glycation endproducts: a multiligand receptor magnifying cell stress in diverse pathologic settings

2002 • 273 citations

Human and Murine ApoE Markedly Alters Aβ Metabolism before and after Plaque Formation in a Mouse Model of Alzheimer's Disease

2002 • 270 citations

Human Apolipoprotein E4 Alters the Amyloid-β 40:42 Ratio and Promotes the Formation of Cerebral Amyloid Angiopathy in an Amyloid Precursor Protein Transgenic Model

2005 • 262 citations

Immunization with a Nontoxic/Nonfibrillar Amyloid-β Homologous Peptide Reduces Alzheimer's Disease-Associated Pathology in Transgenic Mice

2001 • 262 citations

Plaque‐associated disruption of CSF and plasma amyloid‐β (Aβ) equilibrium in a mouse model of Alzheimer's disease

2002 • 255 citations

Fibrillogenesis in Alzheimer's disease of amyloid β peptides and apolipoprotein E

1995 • 255 citations

Plasma amyloid ?-peptide 1-42 and incipient Alzheimer's disease

1999 • 254 citations

Platelet-derived Growth Factor (PDGF)-induced Tyrosine Phosphorylation of the Low Density Lipoprotein Receptor-related Protein (LRP)

2002 • 250 citations

Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer's amyloid β peptides

2000 • 246 citations

Apolipoprotein E ε4 Is Associated With the Presence and Earlier Onset of Hemorrhage in Cerebral Amyloid Angiopathy

1996 • 246 citations

Astrocytes and Microglia Respond to Estrogen with Increased apoE mRNAin Vivoandin Vitro

1997 • 237 citations

Molecular Characterization of a Novel Human Hybrid-type Receptor That Binds the α2-Macroglobulin Receptor-associated Protein

1996 • 236 citations

Human blood-brain barrier receptors for Alzheimer's amyloid-beta 1- 40. Asymmetrical binding, endocytosis, and transcytosis at the apical side of brain microvascular endothelial cell monolayer.

1998 • 232 citations

Apolipoprotein E and cognitive performance

2000 • 225 citations

Fate of Cerebrospinal Fluid‐Borne Amyloid β‐Peptide: Rapid Clearance into Blood and Appreciable Accumulation by Cerebral Arteries

1996 • 223 citations

Alzheimer's Disease Aβ Vaccine Reduces Central Nervous System Aβ Levels in a Non-Human Primate, the Caribbean Vervet

2004 • 218 citations

Glial Fibrillary Acidic Protein–Apolipoprotein E (apoE) Transgenic Mice: Astrocyte-Specific Expression and Differing Biological Effects of Astrocyte-Secreted apoE3 and apoE4 Lipoproteins

1998 • 213 citations

Unique Lipoproteins Secreted by Primary Astrocytes From Wild Type, apoE (−/−), and Human apoE Transgenic Mice

1999 • 207 citations

Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome).

1995 • 207 citations

Elements of Neural Adhesion Molecules and a Yeast Vacuolar Protein Sorting Receptor Are Present in a Novel Mammalian Low Density Lipoprotein Receptor Family Member

1996 • 201 citations

Interaction of Apolipoprotein J-Amyloid β-Peptide Complex with Low Density Lipoprotein Receptor-related Protein-2/Megalin

1997 • 197 citations

A new polymorphism in the APOE promoter associated with risk of developing Alzheimer's disease

1998 • 190 citations

Characterization of stable complexes involving apolipoprotein E and the amyloid β peptide in Alzheimer's disease brain

1995 • 190 citations

Apolipoprotein Eε4 modifies Alzheimer's disease onset in an E280A PS1 kindred

2003 • 185 citations

Clearance of amyloid β-peptide from brain: transport or metabolism?

2000 • 179 citations

Blood-Brain Barrier Transport of Circulating Alzheimer′s Amyloid β

1993 • 170 citations

Is Alzheimer's disease an apolipoprotein E amyloidosis?

1995 • 156 citations

Apolipoprotein E Markedly Facilitates Age-Dependent Cerebral Amyloid Angiopathy and Spontaneous Hemorrhage in Amyloid Precursor Protein Transgenic Mice

2003 • 153 citations

Isoform‐Specific Effects of Apolipoproteins E2, E3, and E4 on Cerebral Capillary Sequestration and Blood‐Brain Barrier Transport of Circulating Alzheimer's Amyloid β

1997 • 144 citations

Apolipoprotein E and the Apolipoprotein E-Deficient Mouse

1995 • 142 citations

The Soluble Form of Alzheimer′s Amyloid β Protein Is Complexed to High Density Lipoprotein 3 and Very High Density Lipoprotein in Normal Human Plasma

1994 • 139 citations

Inhibition of Angiogenesis by A Peptides

2004 • 139 citations

Interaction of Nascent ApoE2, ApoE3, and ApoE4 Isoforms Expressed in Mammalian Cells with Amyloid Peptide β (1−40). Relevance to Alzheimer's Disease

1997 • 135 citations

Brain Uptake of Circulating Apolipoproteins J and E Complexed to Alzheimer′s Amyloid β

1994 • 133 citations

Circulating amyloid-β peptide crosses the blood–brain barrier in aged monkeys and contributes to Alzheimer's disease lesions

2002 • 133 citations

Biochemical Characterization of Alzheimer's Soluble Amyloid Beta Protein in Human Cerebrospinal Fluid: Association with High Density Lipoproteins

1996 • 131 citations

The Low Density Lipoprotein Receptor Regulates the Level of CentralNervous System Human and Murine Apolipoprotein E but Does Not Modify AmyloidPlaque Pathology in PDAPPMice

2005 • 129 citations

The Interaction between Apolipoprotein E and Alzheimer's Amyloid β-Peptide Is Dependent on β-Peptide Conformation

1996 • 129 citations

Differences in the A?40/A?42 ratio associated with cerebrospinal fluid lipoproteins as a function of apolipoprotein E genotype

2000 • 126 citations

Cerebrovascular smooth muscle cells internalize Alzheimer amyloid beta protein via a lipoprotein pathway: implications for cerebral amyloid angiopathy.

1997 • 123 citations

Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-β

2005 • 121 citations

Passage of peptides across the blood-brain barrier: Pathophysiological perspectives

1996 • 119 citations

The conformation of Alzheimer's β peptide determines the rate of amyloid formation and its resistance to proteolysis

1996 • 118 citations

Expression of the Very Low-Density Lipoprotein Receptor (VLDL-r), an Apolipoprotein-E Receptor, in the Central Nervous System and in Alzheimerʼs Disease

1996 • 114 citations

Characterization of the Binding of Amyloid‐β Peptide to Cell Culture‐Derived Native Apolipoprotein E2, E3, and E4 Isoforms and to Isoforms from Human Plasma

1997 • 113 citations

Seeding of Aβ Fibril Formation Is Inhibited by All Three Isotypes of Apolipoprotein E

1996 • 112 citations

Apolipoprotein E promotes the binding and uptake of β-amyloid into Chinese hamster ovary cells in an isoform-specific manner

1999 • 111 citations

Passage of human amyloid β-protein 1–40 across the murine blood-brain barrier

1994 • 109 citations

Substitution at codon 22 reduces clearance of Alzheimer's amyloid-β peptide from the cerebrospinal fluid and prevents its transport from the central nervous system into blood

2002 • 103 citations

APOE genotype and gender effects on Alzheimer disease in 100 adults with Down syndrome

1999 • 101 citations

Dominant negative effects of apolipoprotein E4 revealed in transgenic models of neurodegenerative disease

2000 • 98 citations

Lipoprotein-free amyloidogenic peptides in plasma are elevated in patients with sporadic Alzheimer's disease and Down's syndrome

1999 • 91 citations

Opposite roles of apolipoprotein E in normal brains and in Alzheimer’s disease

1998 • 90 citations

Brain Clearance of Alzheimer's Amyloid-β40 in the Squirrel Monkey: A SPECT Study in a Primate Model of Cerebral Amyloid Angiopathy

2002 • 89 citations

Increased Extracellular Amyloid Deposition and Neurodegeneration in Human Amyloid Precursor Protein Transgenic Mice Deficient in Receptor-Associated Protein

2002 • 89 citations

Amyloid β40/42 clearance across the blood-brain barrier following intra-ventricular injections in wild-type, apoE knock-out and human apoE3 or E4 expressing transgenic mice

2001 • 82 citations

Blood-brain barrier uptake of the 40 and 42 amino acid sequences of circulating Alzheimer's amyloid β in guinea pigs

1996 • 82 citations

Localization of mRNA for low density lipoprotein receptor and a cholesterol synthetic enzyme in rabbit nervous system by in situ hybridization.

1988 • 81 citations

Apolipoprotein E isoform-specific reduction of extracellular amyloid in neuronal cultures

1999 • 77 citations

Identification of a Major Cyclic AMP-Dependent Protein Kinase A Phosphorylation Site within the Cytoplasmic Tail of the Low-Density Lipoprotein Receptor-Related Protein: Implication for Receptor-Mediated Endocytosis

2001 • 74 citations

Nerve Growth Factor Induces Rapid Increases in Functional Cell Surface Low Density Lipoprotein Receptor-related Protein

1998 • 69 citations

The putative blood-brain barrier transporter for the β-amyloid binding protein apolipoprotein j is saturated at physiological concentrations

1997 • 66 citations

Structure and Functions of Human Cerebrospinal Fluid Lipoproteins from Individuals of Different APOE Genotypes

1998 • 64 citations

Detection of Apolipoprotein E/Dimeric Soluble Amyloid β Complexes in Alzheimer's Disease Brain Supernatants

1997 • 59 citations

Phosphorylation of LRP1 Regulation of Transport and Signal Transduction

2002 • 59 citations

Permeability and Residual Plasma Volume of Human, Dutch Variant, and Rat Amyloid β-Protein 1-40 at the Blood–Brain Barrier

1997 • 56 citations

Method for measurement of the blood–brain barrier permeability in the perfused mouse brain: application to amyloid-β peptide in wild type and Alzheimer’s Tg2576 mice

2004 • 54 citations

Intra-arterial infusion of [125l]Aβ 1–40 labels amyloid deposits in the aged primate brain in vivo

1996 • 52 citations

Co-expression of β-amyloid precursor protein (βAPP) and apolipoprotein E in cell culture: analysis of βAPP processing

1995 • 51 citations

Lack of independent associations of apolipoprotein E promoter and intron 1 polymorphisms with Alzheimer's disease

1999 • 39 citations

Amyloid β peptide as a vaccine for Alzheimer's disease involves receptor-mediated transport at the blood–brain barrier

2001 • 31 citations

Apolipoprotein is required for the formation of filamentous amyloid, but not for amorphous Aβ deposition, in an AβPP/PS double transgenic mouse model of Alzheimer's disease

2004 • 14 citations