Biogenesis and metabolism of Alzheimer’s disease Aβ amyloid peptides

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: The Amyloid Cascade Hypothesis

1992 • 6,649 citations

The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor

1987 • 4,544 citations

Amyloid plaque core protein in Alzheimer disease and Down syndrome.

1985 • 4,276 citations

β-Secretase Cleavage of Alzheimer's Amyloid Precursor Protein by the Transmembrane Aspartic Protease BACE

1999 • 3,692 citations

Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse

1999 • 3,112 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

A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain

1999 • 2,051 citations

The carboxy terminus of the .beta. amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimer's disease

1993 • 1,951 citations

Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity

1999 • 1,880 citations

Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein

1998 • 1,786 citations

ER Stress Induces Cleavage of Membrane-Bound ATF6 by the Same Proteases that Process SREBPs

2000 • 1,764 citations

Statins and the risk of dementia

2000 • 1,741 citations

Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids

1992 • 1,701 citations

Alzheimer's disease and Down's syndrome: Sharing of a unique cerebrovascular amyloid fibril protein

1984 • 1,633 citations

Purification and cloning of amyloid precursor protein β-secretase from human brain

1999 • 1,589 citations

Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease

2000 • 1,498 citations

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

1994 • 1,463 citations

Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease

2000 • 1,433 citations

Treatment with a Copper-Zinc Chelator Markedly and Rapidly Inhibits β-Amyloid Accumulation in Alzheimer's Disease Transgenic Mice

2001 • 1,418 citations

Decreased Prevalence of Alzheimer Disease Associated With 3-Hydroxy-3-Methyglutaryl Coenzyme A Reductase Inhibitors

2000 • 1,415 citations

Uber eine eigenartige Erkrankung der Hirnrinde

1907 • 1,332 citations

Regulated Intramembrane Proteolysis

2000 • 1,314 citations

Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red.

1994 • 1,313 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

Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice

1997 • 1,259 citations

Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein

1989 • 1,237 citations

Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons

1998 • 1,139 citations

Constitutive and regulated α-secretase cleavage of Alzheimer’s amyloid precursor protein by a disintegrin metalloprotease

1999 • 1,115 citations

Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease

1988 • 1,098 citations

Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity

1988 • 1,093 citations

Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo

2001 • 1,083 citations

Identification of a Novel Aspartic Protease (Asp 2) as β-Secretase

1999 • 1,072 citations

BACE1 is the major β-secretase for generation of Aβ peptides by neurons

2001 • 1,032 citations

Mice deficient in BACE1, the Alzheimer's β-secretase, have normal phenotype and abolished β-amyloid generation

2001 • 988 citations

Hypercholesterolemia Accelerates the Alzheimer's Amyloid Pathology in a Transgenic Mouse Model

2000 • 984 citations

Evidence That Tumor Necrosis Factor α Converting Enzyme Is Involved in Regulated α-Secretase Cleavage of the Alzheimer Amyloid Protein Precursor

1998 • 922 citations

Metabolic Regulation of Brain Aβ by Neprilysin

2001 • 918 citations

Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and βAPP processing

2000 • 906 citations

Evidence that β-Amyloid Protein in Alzheimer's Disease Is Not Derived by Normal Processing

1990 • 895 citations

Ibuprofen Suppresses Plaque Pathology and Inflammation in a Mouse Model for Alzheimer's Disease

2000 • 880 citations

Functional gamma‐secretase inhibitors reduce beta‐amyloid peptide levels in brain

2001 • 876 citations

Photoactivated γ-secretase inhibitors directed to the active site covalently label presenilin 1

2000 • 861 citations

The cell biology of β-amyloid precursor protein and presenilin in Alzheimer's disease

1998 • 845 citations

Identification of the major Aβ1–42-degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition

2000 • 837 citations

Presenilin is required for activity and nuclear access of Notch in Drosophila

1999 • 801 citations

Insulin-degrading Enzyme Regulates Extracellular Levels of Amyloid β-Protein by Degradation

1998 • 783 citations

Human aspartic protease memapsin 2 cleaves the β-secretase site of β-amyloid precursor protein

2000 • 777 citations

Involvement of Caspases in Proteolytic Cleavage of Alzheimer’s Amyloid-β Precursor Protein and Amyloidogenic Aβ Peptide Formation

1999 • 777 citations

A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimer's disease

2000 • 733 citations

Structure of the Protease Domain of Memapsin 2 (β-Secretase) Complexed with Inhibitor

2000 • 698 citations

Distinct sites of intracellular production for Alzheimer's disease Aβ40/42 amyloid peptides

1997 • 698 citations

Unusual spectral energy distribution of a galaxy previously reported to be at redshift 6.68

2000 • 683 citations

The Amyloid Precursor Protein of Alzheimer's Disease in the Reduction of Copper(II) to Copper(I)

1996 • 657 citations

Amyloid A4 Protein and Its Precursor in Down's Syndrome and Alzheimer's Disease

1989 • 651 citations

Alpha-2 macroglobulin is genetically associated with Alzheimer disease

1998 • 647 citations

Alzheimer's Disease Amyloid-β Binds Copper and Zinc to Generate an Allosterically Ordered Membrane-penetrating Structure Containing Superoxide Dismutase-like Subunits

2001 • 643 citations

TGF-β1 promotes microglial amyloid-β clearance and reduces plaque burden in transgenic mice

2001 • 576 citations

Secretion of β-amyloid precursor protein cleaved at the amino terminus of the β-amyloid peptide

1993 • 546 citations

Estrogen reduces neuronal generation of Alzheimer β-amyloid peptides

1998 • 545 citations

Presenilin 1 is linked with γ-secretase activity in the detergent solubilized state

2000 • 526 citations

Transition-state analogue inhibitors of γ-secretase bind directly to presenilin-1

2000 • 520 citations

Evidence for Genetic Linkage of Alzheimer's Disease to Chromosome 10q

2000 • 513 citations

Mice with Combined Gene Knock-Outs Reveal Essential and Partially Redundant Functions of Amyloid Precursor Protein Family Members

2000 • 485 citations

Aqueous Dissolution of Alzheimer's Disease Aβ Amyloid Deposits by Biometal Depletion

1999 • 481 citations

The Phosphotyrosine Interaction Domains of X11 and FE65 Bind to Distinct Sites on the YENPTY Motif of Amyloid Precursor Protein

1996 • 480 citations

Neurons Regulate Extracellular Levels of Amyloid β-Protein via Proteolysis by Insulin-Degrading Enzyme

2000 • 466 citations

The secreted form of the Alzheimer's amyloid precursor protein with the Kunitz domain is protease nexin-II

1989 • 460 citations

The amyloid protein precursor of Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth

1992 • 455 citations

Alzheimer's Aβ(1–42) is generated in the endoplasmic reticulum/intermediate compartment of NT2N cells

1997 • 443 citations

Alzheimer amyloid protein precursor complexes with brain GTP-binding protein Go

1993 • 430 citations

A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth

1994 • 393 citations

Alzheimer's β‐amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme

1994 • 385 citations

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

2000 • 375 citations

L-685,458, an Aspartyl Protease Transition State Mimic, Is a Potent Inhibitor of Amyloid β-Protein Precursor γ-Secretase Activity

2000 • 366 citations

The presenilins and Alzheimer's disease

1997 • 364 citations

Effects of PS1 Deficiency on Membrane Protein Trafficking in Neurons

1998 • 356 citations

A Novel ε-Cleavage within the Transmembrane Domain of the Alzheimer Amyloid Precursor Protein Demonstrates Homology with Notch Processing

2002 • 349 citations

Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein.

1992 • 343 citations

Modulation of amyloid β-protein clearance and Alzheimer’s disease susceptibility by the LDL receptor–related protein pathway

2000 • 335 citations

Modulation of A beta adhesiveness and secretase site cleavage by zinc.

1994 • 327 citations

Degradation of the Alzheimer's Amyloid β Peptide by Endothelin-converting Enzyme

2001 • 325 citations

The amyloid precursor protein of Alzheimer's disease is released by human platelets.

1990 • 322 citations

Intracellular Generation and Accumulation of Amyloid β-Peptide Terminating at Amino Acid 42

1997 • 302 citations

Post-translational Processing of β-Secretase (β-Amyloid-converting Enzyme) and Its Ectodomain Shedding

2001 • 301 citations

Presenilin-1 and -2 Are Molecular Targets for γ-Secretase Inhibitors

2000 • 300 citations

Platelet Coagulation Factor XI _a -Inhibitor, a Form of Alzheimer Amyloid Precursor Protein

1990 • 299 citations

The Regions of the Fe65 Protein Homologous to the Phosphotyrosine Interaction/Phosphotyrosine Binding Domain of Shc Bind the Intracellular Domain of the Alzheimer's Amyloid Precursor Protein

1995 • 295 citations

Peptidomimetic Probes and Molecular Modeling Suggest That Alzheimer's γ-Secretase Is an Intramembrane-Cleaving Aspartyl Protease

1999 • 290 citations

A novel zinc(II) binding site modulates the function of the beta A4 amyloid protein precursor of Alzheimer's disease

1993 • 289 citations

Inhibition of Amyloid β Protein Aggregation and Neurotoxicity by Rifampicin

1996 • 288 citations

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

2000 • 285 citations

Cell Surface Presenilin-1 Participates in the γ-Secretase-like Proteolysis of Notch

1999 • 268 citations

Membrane-anchored metalloprotease MDC9 has an α-secretase activity responsible for processing the amyloid precursor protein

1999 • 260 citations

The βA4 amyloid precursor protein binding to copper

1994 • 244 citations

Interaction between amyloid precursor protein and presenilins in mammalian cells: Implications for the pathogenesis of Alzheimer disease

1997 • 237 citations

Crystal structure of the N-terminal, growth factor-like domain of Alzheimer amyloid precursor protein.

1999 • 236 citations

Mechanism of the cleavage specificity of Alzheimer’s disease γ-secretase identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein

1999 • 229 citations

Regulation of Amyloid Precursor Protein Cleavage

1999 • 224 citations

The Alzheimer's Disease Amyloid Precursor Protein Modulates Copper-Induced Toxicity and Oxidative Stress in Primary Neuronal Cultures

1999 • 222 citations

Formation of stable complexes between two Alzheimer's disease gene products: Presenilin-2 and β-amyloid precursor protein

1997 • 216 citations

Regulation of β-Amyloid Secretion by FE65, an Amyloid Protein Precursor-binding Protein

1999 • 213 citations

Identification of the Alzheimer beta/A4 amyloid precursor protein in clathrin-coated vesicles purified from PC12 cells.

1993 • 213 citations

Trafficking of cell surface beta-amyloid precursor protein: retrograde and transcytotic transport in cultured neurons.

1995 • 212 citations

Are Presenilins Intramembrane-Cleaving Proteases? Implications for the Molecular Mechanism of Alzheimer's Disease

1999 • 201 citations

What the evolution of the amyloid protein precursor supergene family tells us about its function

2000 • 196 citations

Cell-surface beta-amyloid precursor protein stimulates neurite outgrowth of hippocampal neurons in an isoform-dependent manner

1995 • 196 citations

Cleavage of Alzheimer's Amyloid Precursor Protein by α-Secretase Occurs at the Surface of Neuronal Cells

1999 • 195 citations

The Type 4 Prepilin Peptidases Comprise a Novel Family of Aspartic Acid Proteases

2000 • 187 citations

New protease inhibitors prevent γ-secretase-mediated production of Aβ40/42 without affecting Notch cleavage

2001 • 182 citations

Degradation of Alzheimer's beta-amyloid protein by human and rat brain peptidases: involvement of insulin-degrading enzyme.

1997 • 180 citations

beta-Amyloid precursor protein binds to the neurite-promoting IKVAV site of laminin.

1993 • 180 citations

Secretion of the beta/A4 amyloid precursor protein. Identification of a cleavage site in cultured mammalian cells.

1991 • 178 citations

Unusual phenotypic alteration of β amyloid precursor protein (βAPP) maturation by a new Val-715 → Met βAPP-770 mutation responsible for probable early-onset Alzheimer’s disease

1999 • 174 citations

Proteolytic Processing of the Alzheimer's Disease Amyloid Precursor Protein within Its Cytoplasmic Domain by Caspase-like Proteases

1999 • 172 citations

Regulation of Amyloid Protein Precursor (APP) Binding to Collagen and Mapping of the Binding Sites on APP and Collagen Type I

1996 • 170 citations

Apolipoprotein E and Alzheimer's Disease A Role in Amyloid Catabolism

2000 • 167 citations

Regulated Formation of Golgi Secretory Vesicles Containing Alzheimer β-Amyloid Precursor Protein

1995 • 165 citations

Alternative, Non-secretase Processing of Alzheimer's β-Amyloid Precursor Protein during Apoptosis by Caspase-6 and -8

1999 • 162 citations

The Carboxyl Termini of β-Amyloid Peptides 1-40 and 1-42 Are Generated by Distinct γ-Secretase Activities

1996 • 162 citations

The amyloid precursor protein of Alzheimer’s disease and the Aβ peptide

1999 • 160 citations

Elevated Aβ42 in Skeletal Muscle of Alzheimer Disease Patients Suggests Peripheral Alterations of AβPP Metabolism

2000 • 158 citations

Transgenic Drosophila expressing human amyloid precursor protein show γ-secretase activity and a blistered-wing phenotype

1998 • 155 citations

γ-Secretase, Evidence for Multiple Proteolytic Activities and Influence of Membrane Positioning of Substrate on Generation of Amyloid β Peptides of Varying Length

1999 • 155 citations

Secretion of Alzheimer's disease Abeta amyloid peptide by activated human platelets.

1998 • 153 citations

Study of the synthesis and secretion of normal and artificial mutants of murine amyloid precursor protein (APP): cleavage of APP occurs in a late compartment of the default secretion pathway.

1993 • 152 citations

Presenilins and Alzheimer’s disease: biological functions and pathogenic mechanisms

2000 • 152 citations

Inhibition of β-amyloid formation identifies proteolytic precursors and subcellular site of catabolism

1995 • 148 citations

Interaction of a Neuron-specific Protein Containing PDZ Domains with Alzheimer's Amyloid Precursor Protein

1999 • 146 citations

Amino acid sequence RERMS represents the active domain of amyloid beta/A4 protein precursor that promotes fibroblast growth.

1993 • 143 citations

Intraneuronal compartments of the amyloid precursor protein

1993 • 143 citations

A Novel γ-Secretase Assay Based on Detection of the Putative C-terminal Fragment-γ of Amyloid β Protein Precursor

2001 • 141 citations

Intracellular and secreted Alzheimer β-amyloid species are generated by distinct mechanisms in cultured hippocampal neurons

1997 • 139 citations

α₂‐Macroglobulin Enhances the Clearance of Endogenous Soluble β‐Amyloid Peptide via Low‐Density Lipoprotein Receptor‐Related Protein in Cortical Neuron

1999 • 134 citations

Presenilin complexes with the C-terminal fragments of amyloid precursor protein at the sites of amyloid β-protein generation

2000 • 131 citations

A 109-amino-acid C-terminal fragment of Alzheimer's-disease amyloid precursor protein contains a sequence, -RHDS-, that promotes cell adhesion

1992 • 131 citations

The β-Amyloid Precursor Protein Functions as a Cytosolic Anchoring Site That Prevents Fe65 Nuclear Translocation

2001 • 129 citations

Proteolysis of Aβ Peptide from Alzheimer Disease Brain by Gelatinase A

1994 • 129 citations

Plaque busters: strategies to inhibit amyloid formation in Alzheimer's disease

1999 • 128 citations

Cleavage at the amino and carboxyl termini of Alzheimer's amyloid-beta by cathepsin D

1994 • 126 citations

Insulysin Hydrolyzes Amyloid β Peptides to Products That Are Neither Neurotoxic Nor Deposit on Amyloid Plaques

2000 • 124 citations

Constitutive α‐secretase cleavage of the β‐amyloid precursor protein in the furin‐deficient LoVo cell line: involvement of the pro‐hormone convertase 7 and the disintegrin metalloprotease ADAM10

2001 • 124 citations

Aspartate Mutations in Presenilin and γ‐Secretase Inhibitors Both Impair Notch1 Proteolysis and Nuclear Translocation with Relative Preservation of Notch1 Signaling

2000 • 116 citations

Protease nexin-2/amyloid beta protein precursor. A tight-binding inhibitor of coagulation factor IXa.

1993 • 109 citations

Cell‐free assays for γ‐secretase activity

2000 • 106 citations

Ovariectomy and 17β-estradiol modulate the levels of Alzheimer's amyloid β peptides in brain

2000 • 104 citations

Presenilin 1 Regulates Pharmacologically Distinct γ-Secretase Activities

2000 • 97 citations

β-Amyloid Precursor Protein

1996 • 95 citations

Secreted Glypican Binds to the Amyloid Precursor Protein of Alzheimer's Disease (APP) and Inhibits APP-induced Neurite Outgrowth

1996 • 89 citations

Metalloendopeptidase EC 3.4.24.15 Is Necessary for Alzheimer's Amyloid-β Peptide Degradation

1999 • 86 citations

Purified recombinant insulin-degrading enzyme degrades amyloid β-protein but does not promote its oligomerization

2000 • 84 citations

Chelation and Intercalation: Complementary Properties in a Compound for the Treatment of Alzheimer's Disease

2000 • 82 citations

Amyloid-β Interactions with Chondroitin Sulfate-derived Monosaccharides and Disaccharides

2001 • 81 citations

Alzheimer's disease amyloid precursor protein on the surface of cortical neurons in primary culture co-localizes with adhesion patch components

1996 • 81 citations

Ectodomain Phosphorylation of β-Amyloid Precursor Protein at Two Distinct Cellular Locations

1997 • 79 citations

Candidate .gamma.-Secretases in the Generation of the Carboxyl Terminus of the Alzheimer's Disease .beta.A4 Amyloid: Possible Involvement of Cathepsin D

1995 • 76 citations

The amyloid precursor protein of Alzheimer disease in human brain and blood

1999 • 74 citations

Mice Deficient for the Amyloid Precursor Protein Gene

1996 • 74 citations

A Distinct ER/IC γ-Secretase Competes with the Proteasome for Cleavage of APP

1999 • 73 citations

When Do Epileptic Seizures Really Begin?

2001 • 68 citations

Characterization of the high affinity heparin binding site of the Alzheimer's disease βA4 amyloid precursor protein (APP) and its enhancement by zinc(II)

1995 • 62 citations

Membrane-anchored metalloprotease MDC9 has an α-secretase activity responsible for processing the amyloid precursor protein

1999 • 61 citations

Alzheimer's amyloid precursor protein produced by recombinant baculovirus expression. Proteolytic processing and protease inhibitory properties.

1991 • 54 citations

Proteolytic processing and secretion of human beta-amyloid precursor protein in yeast. Evidence for a yeast secretase activity.

1994 • 54 citations

Retention of the Alzheimer's Amyloid Precursor Fragment C99 in the Endoplasmic Reticulum Prevents Formation of Amyloid β-Peptide

2001 • 54 citations

Subcellular Compartment and Molecular Subdomain of β-Amyloid Precursor Protein Relevant to the Aβ42-promoting Effects of Alzheimer Mutant Presenilin 2

2001 • 53 citations

The multiple paradoxes of presenilins

2001 • 47 citations

Human Brain βA4 Amyloid Protein Precursor of Alzheimer's Disease: Purification and Partial Characterization

1992 • 47 citations

Requirement for Presenilin 1 in Facilitating Jagged 2-Mediated Endoproteolysis and Signaling of Notch 1

2000 • 45 citations

Expression of active secreted forms of human amyloid beta-protein precursor by recombinant baculovirus-infected insect cells.

1991 • 44 citations

Aspartyl Protease Inhibitor Pepstatin Binds to the Presenilins of Alzheimer's Disease

2001 • 42 citations

Isolation of baculovirus-derived secreted and full-length beta-amyloid precursor protein.

1991 • 40 citations

The Pathogenesis of Alzheimer's Disease: Is Amyloid β‐Protein the Beginning or the End?

2000 • 38 citations

Inhibiting Amyloid Precursor Protein C-terminal Cleavage Promotes an Interaction with Presenilin 1

2000 • 38 citations

Mapping the APP/Presenilin (PS) Binding Domains: The Hydrophilic N-Terminus of PS2 Is Sufficient for Interaction with APP and Can Displace APP/PS1 Interaction

1999 • 35 citations

Generation of Alzheimer Amyloid β Peptide through Nonspecific Proteolysis

1997 • 34 citations

Purified recombinant insulin-degrading enzyme degrades amyloid β-protein but does not promote its oligomerization

2000 • 33 citations

Alzheimer’s Disease

1999 • 33 citations

Processing of the Alzheimer's Disease Amyloid Precursor Protein inPichia pastoris: Immunodetection of α-, β-, and γ-Secretase Products

1998 • 27 citations

Regulation of APP Expression, Biogenesis and Metabolism by Extracellular Matrix and Cytokinesa

1996 • 25 citations

The expression and processing of human beta-amyloid peptide precursors in Saccharomyces cerevisiae: evidence for a novel endopeptidase in the yeast secretory system.

1994 • 18 citations

Expression of the Amyloid Precursor Protein of Alzheimer's Disease on the Surface of Transfected HeLa Cells

1995 • 13 citations

Platelets and DAMI megakaryocytes possess β-secretase-like activity

1999 • 12 citations

The role of presenilins in γ‐secretase activity: catalyst or cofactor?

2001 • 11 citations

Presenilin 1 expression in yeast lowers secretion of the amyloid precursor protein

2000 • 6 citations

Return from the brink of death

2001 • 1 citations