The endosomal-lysosomal system of neurons in Alzheimer's disease pathogenesis: a review.

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

1993 • 8,888 citations

Caspases: the executioners of apoptosis

1997 • 4,674 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

Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene

1995 • 2,028 citations

Amyloid β-peptide is produced by cultured cells during normal metabolism

1992 • 1,888 citations

The proto-oncogene Bcl-2 and its role in regulating apoptosis

1997 • 1,768 citations

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

1996 • 1,467 citations

Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1

1996 • 1,439 citations

The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway

1992 • 1,342 citations

An endothelial receptor for oxidized low-density lipoprotein

1997 • 1,334 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

Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments

1990 • 1,150 citations

EEA1 links PI(3)K function to Rab5 regulation of endosome fusion

1998 • 1,101 citations

rab5 controls early endosome fusion in vitro

1991 • 1,090 citations

Endoproteolysis of Presenilin 1 and Accumulation of Processed Derivatives In Vivo

1996 • 1,013 citations

Evidence that production and release of amyloid beta-protein involves the endocytic pathway

1994 • 984 citations

BAX-induced cell death may not require interleukin 1β-converting enzyme-like proteases

1996 • 911 citations

Apolipoprotein E allele–specific antioxidant activity and effects on cytotoxicity by oxidative insults and β–amyloid peptides

1996 • 876 citations

Normal and Abnormal Biology of the beta-Amyloid Precursor Protein

1994 • 813 citations

Endocytic Pathway Abnormalities Precede Amyloid β Deposition in Sporadic Alzheimer’s Disease and Down Syndrome

2000 • 764 citations

Tau protein and the neurofibrillary pathology of Alzheimer's disease

1993 • 710 citations

APOLIPOPROTEIN E ALLELES AS RISK FACTORS IN ALZHEIMER'S DISEASE

1996 • 677 citations

The small GTP-binding protein rab4 controls an early sorting event on the endocytic pathway

1992 • 648 citations

Alpha-2 macroglobulin is genetically associated with Alzheimer disease

1998 • 647 citations

A New Function for the LDL Receptor: Transcytosis of LDL across the Blood–Brain Barrier

1997 • 531 citations

β-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer's disease

1993 • 520 citations

Cytochrome c in the apoptotic and antioxidant cascades

1998 • 491 citations

Rabaptin-5 is a direct effector of the small GTPase Rab5 in endocytic membrane fusion

1995 • 476 citations

Cathepsin D protease mediates programmed cell death induced by interferon-gamma, Fas/APO-1 and TNF-alpha.

1996 • 467 citations

Dementia of the Alzheimer Type

1981 • 451 citations

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

1997 • 443 citations

Participation of Presenilin 2 in Apoptosis: Enhanced Basal Activity Conferred by an Alzheimer Mutation

1996 • 424 citations

Physiological production of the β-amyloid protein and the mechanism of Alzheimer's disease

1993 • 423 citations

Increased neuronal endocytosis and protease delivery to early endosomes in sporadic Alzheimer's disease: neuropathologic evidence for a mechanism of increased beta-amyloidogenesis.

1997 • 388 citations

Mutagenesis Identifies New Signals for β-Amyloid Precursor Protein Endocytosis, Turnover, and the Generation of Secreted Fragments, Including Aβ42

1999 • 381 citations

Cathepsin D targeted by acid sphingomyelinase-derived ceramide

1999 • 361 citations

Gene expression and cellular content of cathepsin D in Alzheimer's disease brain: Evidence for early up-regulation of the endosomal-lysosomal system

1995 • 359 citations

Association of interleukin-1 gene polymorphisms with Alzheimer's disease

2000 • 358 citations

Rab4 and cellubrevin define different early endosome populations on the pathway of transferrin receptor recycling.

1996 • 338 citations

Association of early-onset Alzheimer's disease with an interleukin-1? gene polymorphism

2000 • 331 citations

The human entorhinal cortex: normal morphology and lamina-specific pathology in various diseases

1992 • 320 citations

Photo-Oxidative Disruption of Lysosomal Membranes Causes Apoptosis of Cultured Human Fibroblasts

1997 • 282 citations

Loss of endosomal/lysosomal membrane impermeability is an early event in amyloid A?1-42 pathogenesis

1998 • 277 citations

Generation of Alzheimer β-amyloid protein in the trans-Golgi network in the apparent absence of vesicle formation

1997 • 271 citations

Caspase-Mediated Fragmentation of Calpain Inhibitor Protein Calpastatin during Apoptosis

1998 • 270 citations

Oxidative stress causes relocation of the lysosomal enzyme cathepsin D with ensuing apoptosis in neonatal rat cardiomyocytes.

1998 • 263 citations

REVIEWThe Gene Defects Responsible for Familial Alzheimer's Disease

1996 • 262 citations

Apolipoprotein E genotyping in the differential diagnosis, not prediction, of Alzheimer's disease

1995 • 253 citations

Lysosomal hydrolases of different classes are abnormally distributed in brains of patients with Alzheimer disease.

1991 • 249 citations

Potential role for Cathepsin D in p53-dependent tumor suppression and chemosensitivity

1998 • 229 citations

Lysosomal release of Cathepsin D precedes relocation of Cytochrome C and loss of mitochondrial transmembrane potential during apoptosis induced by oxidative stress

1999 • 226 citations

Lysosomal abnormalities in degenerating neurons link neuronal compromise to senile plaque development in Alzheimer disease

1994 • 214 citations

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

1999 • 213 citations

Peptidyl diazomethyl ketones are specific inactivators of thiol proteinases.

1981 • 208 citations

Apolipoprotein E and the CNS Response to Injury

1998 • 205 citations

Inhibition of ischaemic hippocampal neuronal death in primates with cathepsin B inhibitor CA‐074: a novel strategy for neuroprotection based on ‘calpain–cathepsin hypothesis’

1998 • 204 citations

Apolipoprotein E and cognitive change in an elderly population

1996 • 202 citations

Presenilins and Alzheimer disease

1995 • 193 citations

Molecular aspects of the endocytic pathway

1998 • 193 citations

Identification and characterization of cells deficient in the mannose 6-phosphate receptor: evidence for an alternate pathway for lysosomal enzyme targeting.

1983 • 186 citations

Genetics and molecular advances in Alzheimer's disease

1993 • 183 citations

Cleavage of Alzheimer's Amyloid Precursor Protein (APP) by Secretases Occurs after O-Glycosylation of APP in the Protein Secretory Pathway

1998 • 182 citations

Mr 46,000 mannose 6-phosphate specific receptor: its role in targeting of lysosomal enzymes.

1987 • 174 citations

Isoform-specific effect of apolipoprotein E on cell survival and beta-amyloid-induced toxicity in rat hippocampal pyramidal neuronal cultures.

1998 • 172 citations

Presenilin 1 Regulates the Processing of β-Amyloid Precursor Protein C-Terminal Fragments and the Generation of Amyloid β-Protein in Endoplasmic Reticulum and Golgi

1998 • 171 citations

Lysosomal proteinase antigens are prominently localized within senile plaques of Alzheimer's disease: evidence for a neuronal origin

1990 • 168 citations

Genetic association of an ( 2-macroglobulin (Val1000lle) polymorphism and Alzheimer's disease

1998 • 161 citations

The thiol crosslinking agent diamide overcomes the apoptosis-inhibitory effect of Bcl-2 by enforcing mitochondrial permeability transition

1998 • 155 citations

Caspase Dependent DNA Fragmentation Might Be Associated with Excitotoxicity in Alzheimer Disease

1998 • 155 citations

Regulation of a novel pathway for cell death by lysosomal aspartic and cysteine proteinases

1999 • 153 citations

The involvement of the small GTP-binding protein Rab5a in neuronal endocytosis

1994 • 152 citations

Association of Mouse Actin-binding Protein 1 (mAbp1/SH3P7), an Src Kinase Target, with Dynamic Regions of the Cortical Actin Cytoskeleton in Response to Rac1 Activation

2000 • 149 citations

Molecular Mechanisms of Endocytosis

1997 • 147 citations

Apoptosis caused by oxidized LDL is manganese superoxide dismutase and p53 dependent

1998 • 136 citations

The endosomal-lysosomal system of neurons: new roles

1995 • 136 citations

Novel β-Secretase Cleavage of β-Amyloid Precursor Protein in the Endoplasmic Reticulum/Intermediate Compartment of NT2N Cells

1997 • 135 citations

Bcl-2 Family Proteins: Strategies for Overcoming Chemoresistance in Cancer

1997 • 127 citations

Quantitative Decrease in Synaptophysin Message Expression and Increase in Cathepsin D Message Expression in Alzheimer Disease Neurons Containing Neurofibrillary Tangles

1999 • 125 citations

Familial and sporadic Alzheimer's disease

1996 • 125 citations

The Baxα:Bcl-2 ratio modulates the response to dexamethasone in leukaemic cells and is highly variable in childhood acute leukaemia

1997 • 125 citations

Uptake of Oxidized LDL by Macrophages Results in Partial Lysosomal Enzyme Inactivation and Relocation

1998 • 121 citations

Non-selective autophagy.

1990 • 118 citations

Participation of Cathepsins B and D in Apoptosis of PC12 Cells Following Serum Deprivation

1998 • 118 citations

Regulation and Expression of the Alzheimer's β/A4 Amyloid Protein Precursor in Health, Disease, and Down's Syndromea

1993 • 115 citations

Heterologous transmembrane and cytoplasmic domains direct functional chimeric influenza virus hemagglutinins into the endocytic pathway.

1986 • 114 citations

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

1996 • 112 citations

Elevated Levels of the Endosomal‐Lysosomal Proteinase Cathepsin D in Cerebrospinal Fluid in Alzheimer Disease

1995 • 105 citations

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

1999 • 101 citations

Inhibition of Cathepsin D Prevents Free-Radical-Induced Apoptosis in Rat Cardiomyocytes

2000 • 98 citations

A genetic variation of cathepsin D is a major risk factor for Alzheimer's disease

2000 • 98 citations

Protective effect of 17β-estradiol against the cytotoxicity of minimally oxidized LDL to cultured bovine aortic endothelial cells

1993 • 93 citations

Activation of caspase-3 and apoptosis in cerebellar granule cells

1998 • 88 citations

A Possible Role for Cathepsins D, E, and B in the Processing of β‐amyloid Precursor Protein in Alzheimer's Disease

1997 • 87 citations

The Lysosomal System in Neuronal Cell Death: A Review^a

1993 • 83 citations

Suppression of Cathepsins B and L Causes a Proliferation of Lysosomes and the Formation of Meganeurites in Hippocampus

1997 • 82 citations

46-kDa Mannose 6-phosphate-Specific Receptor: Biosynthesis, Processing, Subcellular Location and Topology

1987 • 80 citations

Genetic association studies between Alzheimer's disease and two polymorphisms in the low density lipoprotein receptor-related protein gene

1998 • 80 citations

Association between the low density lipoprotein receptor-related protein (LRP) and Alzheimer's disease

1997 • 77 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

Apolipoprotein E Binds to and Potentiates the Biological Activity of Ciliary Neurotrophic Factor

1997 • 76 citations

Cathepsin D displays in vitro β-secretase-like specificity

1997 • 75 citations

Genetic polymorphism of cathepsin D is strongly associated with the risk for developing sporadic Alzheimer's disease

1999 • 74 citations

Colocalization of Lysosomal Hydrolase and β-Amyloid in Diffuse Plaques of the Cerebellum and Striatum in Alzheimerʼs Disease and Downʼs Syndrome

1996 • 73 citations

Late Compartments of Amyloid Precursor Protein Transport in SY5Y Cells Are Involved in β-Amyloid Secretion

1997 • 69 citations

Developmental Regulation of Presenilin-1 Processing in the Brain Suggests a Role in Neuronal Differentiation

1997 • 67 citations

The human FE65 gene: genomic structure and an intronic biallelic polymorphism associated with sporadic dementia of the Alzheimer type

1998 • 66 citations

Antioxidant protection of LDL by physiologic concentrations of estrogens is specific for 17-beta-estradiol

1998 • 65 citations

Relative efficacies of amyloid ? peptide (A?) binding proteins in A? aggregation

1996 • 65 citations

Anomalous accumulation of τ and ubiquitin immunoreactivities in rat brain caused by protease inhibition and by normal aging: a clue to PHF pathogenesis?

1989 • 65 citations

ApoE genotype is a risk factor in nonpresenilin early-onset alzheimer's disease families

1998 • 63 citations

Processing of the Pre‐β‐amyloid Protein by Cathepsin <scp>d</scp> is Enhanced by a Familial Alzheimer's Disease Mutation

1994 • 63 citations

Differential Localization of Cysteine Protease Inhibitors and a Target Cysteine Protease, Cathepsin B, by Immuno-Confocal Microscopy

1998 • 60 citations

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

1997 • 59 citations

On the metabolism of apolipoprotein E and the Alzheimer diseases

1995 • 57 citations

Missense polymorphism (C/T224) in the human cathepsin D pro-fragment determined by polymerase chain reaction—Single strand conformational polymorphism analysis and possible consequences in cancer cells

1994 • 55 citations

Cell and molecular neurobiology of presenilins: A role for the endoplasmic reticulum in the pathogenesis of Alzheimer's disease?

1997 • 54 citations

The synchronization between brain areas under motor inhibition process in humans estimated by event-related EEG coherence

1998 • 45 citations

Association between bleomycin hydrolase and Alzheimer's disease in caucasians

1998 • 43 citations

Prevalence of Dementia ofAlzheimer Type and Apolipoprotein EPhenotypes in Aged Patients withDown’s Syndrome

1998 • 41 citations

Genetic Risk Factors in Japanese Alzheimer’s Disease Patients: α1-ACT, VLDLR, and ApoE

1998 • 40 citations

APOE -491 promoter polymorphism is a risk factor for late-onset Alzheimer's disease

1999 • 38 citations

Cathepsin D gene exon 2 polymorphism and sporadic Alzheimer's disease

1999 • 36 citations

Oxidant-induced apoptosis: a consequence of lethal lysosomal leak?

1997 • 35 citations

Cell death induced by peroxidized low-density lipoprotein: endopepsis.

1994 • 32 citations

Identification of the lrp gene in Bradyrhizobium japonicum and its role in regulation of delta-aminolevulinic acid uptake

1997 • 18 citations

Lysosomal Dysfunction Reduces Brain-Derived Neurotrophic Factor Expression

1998 • 15 citations

Ethanol-impaired hepatic protein trafficking: concepts from the asialoglycoprotein receptor system

1999 • 14 citations

Protease activities in normal and schizophrenic human prefrontal cortex and white matter

1981 • 9 citations

Vitamin E Protects Human Aortic Endothelial Cells from Cytotoxic Injury Induced by Oxidized LDL In Vitro 11This project has been funded at least in part with Federal funds from the U.S. Department of Agriculture, Agricultural Research Service under contract number 53-K06-01. The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. …

1998 • 8 citations