The possible place of cathepsins and cystatins in the puzzle of Alzheimer disease

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

1987 • 4,544 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

Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology.

1986 • 3,430 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

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

1992 • 1,888 citations

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

1992 • 1,701 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

Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing

1992 • 1,438 citations

Cleavage of Amyloid β Peptide During Constitutive Processing of Its Precursor

1990 • 1,388 citations

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

1989 • 1,237 citations

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

1988 • 1,098 citations

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

1994 • 984 citations

Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs.

1992 • 982 citations

Neurotoxicity of a Fragment of the Amyloid Precursor Associated with Alzheimer's Disease

1989 • 904 citations

Immunochemical identification of the serine protease inhibitor α1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease

1988 • 899 citations

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

1990 • 895 citations

Targeting of cell-surface β-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments

1992 • 883 citations

Normal and Abnormal Biology of the beta-Amyloid Precursor Protein

1994 • 813 citations

Processing of the Amyloid Protein Precursor to Potentially Amyloidogenic Derivatives

1992 • 737 citations

Beta-amyloid precursor protein cleavage by a membrane-bound protease.

1992 • 726 citations

Generation of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells.

1993 • 557 citations

Induction of Alzheimer-like β-Amyloid Immunoreactivity in the Brains of Rabbits with Dietary Cholesterol

1994 • 549 citations

Isolation of six cysteine proteinase inhibitors from human urine. Their physicochemical and enzyme kinetic properties and concentrations in biological fluids.

1986 • 499 citations

Amyloid β Protein Enhances the Survival of Hippocampal Neurons in Vitro

1989 • 470 citations

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

1989 • 460 citations

Protease nexin-II, a potent anti-chymotrypsin, shows identity to amyloid β-protein precursor

1989 • 437 citations

Enzymatically active lysosomal proteases are associated with amyloid deposits in Alzheimer brain.

1990 • 415 citations

Amyloid peptides are toxic via a common oxidative mechanism.

1995 • 372 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

Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of gamma-trace basic protein (cystatin C).

1986 • 332 citations

Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes

1991 • 297 citations

Alzheimer's disease: a cell biological perspective

1992 • 274 citations

Inhibitors of Lysosomal Enzymes: Accumulation of Lipofuscin-Like Dense Bodies in the Brain

1984 • 274 citations

Localization of Alzheimer βA4 amyloid precursor protein at central and peripheral synaptic sites

1991 • 259 citations

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

1991 • 249 citations

Proteases and proteolysis in the lysosome

1992 • 240 citations

Intracellular accumulation and resistance to degradation of the Alzheimer amyloid A4/beta protein.

1992 • 231 citations

Alzheimer paired helical filaments: Bulk isolation, solubility, and protein composition

1984 • 227 citations

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

1994 • 214 citations

Chloroquine inhibits intracellular degradation but not secretion of Alzheimer beta/A4 amyloid precursor protein.

1992 • 202 citations

Morphologic and biochemical analysis of the intracellular trafficking of the Alzheimer beta/A4 amyloid precursor protein

1994 • 175 citations

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

1990 • 168 citations

Fine structural localization of acid phosphatase in senile plaques in Alzheimer's presenile dementia

1967 • 163 citations

Amyloidogenicity of rodent and human βA4 sequences

1993 • 155 citations

Neurofilament Accumulation Induced in Synapses by Leupeptin

1983 • 154 citations

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

1995 • 148 citations

The amyloid precursor protein is concentrated in neuronal lysosomes in normal and Alzheimer disease subjects

1989 • 142 citations

The Alzheimer β-amyloid protein precursor/protease nexin-II is cleaved by secretase in a trans-Golgi secretory compartment in human neuroglioma cells

1993 • 141 citations

α1-Antitrypsin and α1-antichymotrypsin are in the lesions of Alzheimerʼs disease

1992 • 128 citations

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

1994 • 126 citations

Protein Degradation in Health and Disease

1981 • 124 citations

Evidence for lysosomal processing of amyloid ?-protein precursor in cultured cells

1989 • 114 citations

Detection of lysosomal cysteine proteinases in microglia: Flow cytometric measurement and histochemical localization of cathepsin B and L

1993 • 109 citations

Abnormal distribution of cathepsins in the brain of patients with Alzheimer's disease

1991 • 108 citations

The lysosomal cysteine protease, cathepsin S, is increased in Alzheimer's disease and Down syndrome brain. An immunocytochemical study.

1995 • 108 citations

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

1995 • 105 citations

Alzheimer beta/A4 amyloid precursor protein in human brain: aging-associated increases in holoprotein and in a proteolytic fragment.

1991 • 105 citations

Phagocytosis of ?/A4 amyloid fibrils of the neuritic neocortical plaques

1991 • 104 citations

The Lysosomal System in Neurons

1992 • 102 citations

Abnormal distribution of cathepsin proteinases and endogenous inhibitors (cystatins) in the hippocampus of patients with Alzheimer's disease, parkinsonism-dementia complex on Guam, and senile dementia and in the aged

1993 • 95 citations

Apolipoprotein E ε2 allele promotes longevity and protects patients with Downʼs syndrome from dementia

1994 • 91 citations

Interaction between the zinc(II) and the heparin binding site of the Alzheimer's disease βA4 amyloid precursor protein (APP)

1994 • 89 citations

Production of thrombin and antithrombin III by brain and astroglial cell cultures

1991 • 88 citations

Reactive microglia/macrophages phagocytose amyloid precursor protein produced by neurons following neural damage

1992 • 87 citations

Processing of the beta-amyloid precursor. Multiple proteases generate and degrade potentially amyloidogenic fragments

1993 • 87 citations

Chloroquine inhibits intracellular segradation but not decretion of Alzheimerβ/A4 amyloid precursor protein.

1992 • 80 citations

Age-related increase in a cathepsin D-like protease that degrades brain microtubule-associated proteins

1987 • 80 citations

Degradation of Neurofilament Proteins by Purified Human Brain Cathepsin D

1984 • 80 citations

The role of a cathepsin D-like activity in the release of Galβ1-4GlcNAc α2-6-sialyltransferase from rat liver Golgi membranes during the acute-phase response

1988 • 79 citations

An overview of protease specificity and catalytic mechanisms: aspects related to nomenclature and classification

1985 • 77 citations

Amyloid precursor protein secretion and βA4 amyloid generation are not mutually exclusive

1994 • 75 citations

Tau Proteins Are Abnormally Expressed in Olfactory Epithelium of Alzheimer Patients and Developmentally Regulated in Human Fetal Spinal Cord

1993 • 74 citations

Induction of β-Amyloid-Containing Polypeptides in Hippocampus: Evidence for a Concomitant Loss of Synaptic Proteins and Interactions with an Excitotoxin

1994 • 72 citations

Lysosome instability in aged rat brain

1989 • 71 citations

Mechanism of neurofibrillary degeneration in Alzheimer's disease

1994 • 70 citations

The microtubule-associated protein tau forms a triple-stranded left-hand helical polymer.

1991 • 66 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

Immunoreactivity of neuronal lipofuscin with monoclonal antibodies to the amyloid β-protein

1989 • 64 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

Cathepsin D inactivates cysteine proteinase inhibitors cystatins

1988 • 61 citations

Novel monocyte-like properties of microglial/astroglial cells. Constitutive secretion of lysozyme and cystatin-C.

1987 • 59 citations

Subcellular localization and targeting of cathepsin E.

1994 • 59 citations

Acid hydrolases in early and late endosome fractions from rat liver.

1991 • 58 citations

Inhibition of proteolysis blocks anterograde-retrograde conversion of axonally transported vesicles

1988 • 58 citations

Evidence for a nonsecretory, acidic degradation pathway for amyloid precursor protein in 293 cells. Identification of a novel, 22-kDa, beta-peptide-containing intermediate.

1992 • 56 citations

Immunodetection of cathepsin D in neuritic plaques found in brains of patients with dementia of Alzheimer type.

1989 • 53 citations

The breakdown of the individual neurofilament proteins by cathepsin D

1987 • 52 citations

Serine protease inhibitor antithrombin III and its messenger RNA in the pathogenesis of Alzheimer's disease.

1993 • 49 citations

Processing of Alzheimer Aβ-Amyloid Precursor Protein: Cell Biology, Regulation, and Role in Alzheimer Disease

1994 • 49 citations

Immunocytochemical evidence that the beta-protein precursor is an integral component of neurofibrillary tangles of Alzheimer's disease.

1993 • 46 citations

Antigenic expression of cathepsin B in aged human brain

1990 • 43 citations

An immunohistochemical study of cathepsin E in Alzheimer-type dementia brains

1994 • 43 citations

Inhibition of apolipoprotein E degradation in a post-Golgi compartment by a cysteine protease inhibitor.

1993 • 40 citations

Hereditary cerebral hemorrhage with amyloidosis (Dutch): a model for congophilic plaque formation without neurofibrillary pathology

1994 • 37 citations

Calpain activity in adult and aged human brain regions

1994 • 36 citations

Protease inhibitors generate cytotoxic fragments from alzheimer amyloid protein precursor in cDNA-transfected glioma cells

1992 • 33 citations

An Endosomal‐Lysosomal Pathway for Degradation of Amyloid Precursor Protein ^a

1992 • 33 citations

Amyloidosis in aging and Alzheimer's disease.

1992 • 32 citations

Proteolysis of Microtubule‐Associated Protein 2 and Tubulin by Cathepsin D

1991 • 31 citations

Purification and characterization of a cathepsin D protease from bovine chromaffin granules

1992 • 30 citations

β-amyloid precursor protein fragments and lysosomal dense bodies are found in rat brain neurons after ventricular infusion of leupeptin

1994 • 29 citations

Normal Processing of the Alzheimer's Disease Amyloid β Protein Precursor Generates Potentially Amyloidogenic Carboxyl‐Terminal Derivatives

1992 • 28 citations

Cystatin a-like immunoreactivity is widely distributed in human brain and accumulates in neuritic plaques of alzheimer disease subjects

1994 • 24 citations

[16] Purification of tau protein from brain

1986 • 24 citations

Hydrolysis of amyloid precursor protein-derived peptides by cysteine proteinases and extracts of rat brain clathrin-coated vesicles

1994 • 24 citations

Production of Alzheimer 4-kDa β-Amyloid Peptide Requires the C-Terminal Cytosolic Domain of the Amyloid Precursor Protein

1994 • 22 citations

Reversal of rapid axonal transport at a lesion: leupeptin inhibits reversed protein transport, but does not inhibit reversed organelle transport

1991 • 21 citations

Differential expression of carboxyl terminal derivatives of amyloid precursor protein among cell lines

1992 • 21 citations

Potentially amyloidogenic fragment of 50 kDa and intracellular processing of amyloid precursor protein in cells cultured under leupeptin

1994 • 20 citations

Isolation and characterization of periaxolemmal and axolemmal enriched membrane fractions from the rat central nervous system

1992 • 19 citations

Demonstration of an active component of inter-α-trypsin inhibitor in the brains of Alzheimer type dementia

1991 • 19 citations

Leupeptin as a tool for the detection of the sites of catabolism of rat high-density lipoprotein apolipoproteins A-I and E

1985 • 19 citations

Characterization of proteases with the specificity to cleave at the secretase-site of β-APP

1993 • 17 citations

Isolation of a Membrane-Associated Cathepsin D-like Enzyme from the Model Antigen Presenting Cell, A20, and Its Ability to Generate Antigenic Fragments from a Protein Antigen in a Cell-Free System

1993 • 15 citations

Lysosomal proteinases as putative diagnostic tools in human neuropathology: Alzheimer disease (AD) and schizophrenia.

1992 • 14 citations

Inhibitors of endocytosis, endosome fusion, and lysosomal processing inhibit the intracellular proteolysis of the amyloid precursor protein

1993 • 14 citations

[Apolipoprotein E and Alzheimer dementia. Personal results and brief literature review].

1994 • 9 citations

The Cystatin-C gene is not linked to early onset familial Alzheimer's disease

1993 • 8 citations

Amyloidogenesis in Alzheimer's disease

1993 • 8 citations

Ultrastructural Study of Cathepsin B Immunoreactivity in Rat Brain Neurons: Lysosomal and Extralysosomal Localizations of the Antigen

1991 • 6 citations

Identification of 5.8 kDa C-terminal fragments of Alzheimer amyloid p protein precursor generated in the lysosomal system

1994 • 3 citations

The many faces of lysosomal proteinases (cathepsins) in human neuropathology. A histochemical perspective.

1994 • 2 citations

DOE opens doors to SSC proposals

1994 • 2 citations

Research and development challenges for Alzheimer's disease drug discovery

1994 • 1 citations

ALZHEIMER'S DISEASE: A LYSOSOMAL DISORDER?

1994 • 1 citations