Scholars@Duke
Warren James Strittmatter

Warren James Strittmatter

Professor Emeritus of Neurology
Neurology, Behavioral Neurology
warren@neuro.duke.edu
Duke Box 2900, Durham, NC 27710
227H Bryan Res Bldg, Durham, NC 27710

Selected Publications

Inhibition of protein misfolding/aggregation using polyglutamine binding peptide QBP1 as a therapy for the polyglutamine diseases.

Journal Article Neurotherapeutics · July 2013 Protein misfolding and aggregation in the brain have been recognized to be crucial in the pathogenesis of various neurodegenerative diseases, including Alzheimer's, Parkinson's, and the polyglutamine (polyQ) diseases, which are collectively called the "pro ... Full text Link to item Cite

Bathing the brain.

Journal Article J Clin Invest · March 2013 The brain and spinal cord are surrounded by cerebrospinal fluid, which provides a mechanically stable environment for these delicate structures against the forces of gravity and sudden acceleration and deceleration. Neurons and glia comprising the parenchy ... Full text Link to item Cite

Alzheimer’s disease: the new promise.

Journal Article J Clin Invest · April 2012 Clinical vignette: A 59-year-old aeronautical engineer is referred to you for evaluation because of increasing difficulty with job performance over the last several years. Difficulty managing home finances, getting lost driving, and forgetting appointments ... Full text Link to item Cite

Utility of a simple algorithm to grade diastolic dysfunction and predict outcome after coronary artery bypass graft surgery.

Journal Article Ann Thorac Surg · June 2011 BACKGROUND: Inclusion of a measure of left ventricular diastolic dysfunction (LVDD) may improve risk prediction after cardiac surgery. Current LVDD grading guidelines rely on echocardiographic variables that are not always available or aligned to allow gra ... Full text Link to item Cite

Genome-wide scan of copy number variation in late-onset Alzheimer's disease.

Journal Article J Alzheimers Dis · 2010 Alzheimer's disease is a complex and progressive neurodegenerative disease leading to loss of memory, cognitive impairment, and ultimately death. To date, six large-scale genome-wide association studies have been conducted to identify SNPs that influence d ... Full text Open Access Link to item Cite

A genome-wide investigation of SNPs and CNVs in schizophrenia.

Journal Article PLoS Genet · February 2009 We report a genome-wide assessment of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) in schizophrenia. We investigated SNPs using 871 patients and 863 controls, following up the top hits in four independent cohorts comprising 1,460 ... Full text Link to item Cite

Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia.

Journal Article Leukemia · December 2008 Survival of chronic lymphocytic leukemia (CLL) cells requires sustained activation of the antiapoptotic PI-3-K/Akt pathway, and many therapies for CLL cause leukemia cell death by triggering apoptosis. Blood lipoprotein particles are either pro- or antiapo ... Full text Link to item Cite

Identification of chemical inhibitors to human tissue transglutaminase by screening existing drug libraries.

Journal Article Chem Biol · September 22, 2008 Human tissue transglutaminase (TGM2) is a calcium-dependent crosslinking enzyme involved in the posttranslational modification of intra- and extracellular proteins and implicated in several neurodegenerative diseases. To find specific inhibitors to TGM2, t ... Full text Link to item Cite

Mortalin is regulated by APOE in hippocampus of AD patients and by human APOE in TR mice.

Journal Article Neurobiol Aging · December 2007 Mortalin is a chaperone protein associated with cell survival, stress response, intracellular trafficking, control of cell proliferation, mitochondrial biogenesis, and cell fate determination. Human APOE targeted replacement (TR) mice have been used to elu ... Full text Link to item Cite

Optimization of a polyglutamine aggregation inhibitor peptide (QBP1) using a thioflavin T fluorescence assay.

Journal Article Assay Drug Dev Technol · October 2007 Polyglutamine protein aggregates are a hallmark of several neurodegenerative diseases, including Huntington's disease, and increasing evidence suggests that reducing or inhibiting aggregation produces a therapeutic benefit in animal models of disease. Part ... Full text Link to item Cite

High-fat/high-cholesterol diet promotes a S1P receptor-mediated antiapoptotic activity for VLDL.

Journal Article J Lipid Res · April 2007 Withdrawing growth factors or serum from endothelial cells leads to the activation of effector caspases 3 and 7, resulting in apoptotic cell death. HDL protects against caspase induction through sphingosine-1-phosphate (S1P) receptors. This anti-caspase ac ... Full text Link to item Cite

Apolipoprotein E alleles and sensorineural hearing loss.

Journal Article Int J Audiol · April 2007 The purpose of this paper is to determine if a relationship exists between APOE alleles and nonsyndromic, sensorineural hearing loss (SNHL) in adults. APOE genotype was determined on DNA obtained from a sample of 89 subjects with nonsyndromic, adult onset ... Full text Link to item Cite

APOE4-VLDL inhibits the HDL-activated phosphatidylinositol 3-kinase/Akt Pathway via the phosphoinositol phosphatase SHIP2.

Journal Article Circ Res · October 13, 2006 Endothelial cell dysfunction and apoptosis are critical in the pathogenesis of atherosclerotic cardiovascular disease (CVD). Both endothelial cell apoptosis and atherosclerosis are reduced by high-density lipoprotein (HDL). Low HDL levels increase the risk ... Full text Link to item Cite

APOE2 allele increased in tardive dyskinesia.

Journal Article Mov Disord · April 2006 Ninety-seven inpatients with tardive dyskinesia (average AIMS score = 13), the majority of whom were schizophrenic, were studied. Forty patients were Caucasian, and 57 were African-American. The APOE genotypes of these patients were compared to previously ... Full text Link to item Cite

Polyglutamine expansion inhibits respiration by increasing reactive oxygen species in isolated mitochondria.

Journal Article Biochem Biophys Res Commun · March 10, 2006 Huntington's disease results from expansion of the polyglutamine (PolyQ) domain in the huntingtin protein. Although the cellular mechanism by which pathologic-length PolyQ protein causes neurodegeneration is unclear, mitochondria appear central in pathogen ... Full text Link to item Cite

Phage display screening for peptides that inhibit polyglutamine aggregation.

Journal Article Methods Enzymol · 2006 Proteins with expanded polyglutamine domains cause nine dominantly inherited, neurodegenerative diseases, including Huntington's disease. There are no therapies that inhibit disease onset or progression. To identify a novel therapeutic, we screened phage d ... Full text Link to item Cite

Disrupted spermine homeostasis: a novel mechanism in polyglutamine-mediated aggregation and cell death.

Journal Article J Neurosci · August 11, 2004 Our data suggest a novel mechanism whereby pathological-length polyglutamine (polyQ) proteins promote the spermine synthetic pathway, increasing polyQ-aggregation and cell death. As detected in a cell-free turbidity assay, spermine promotes aggregation of ... Full text Link to item Cite

Disruption of the toxic conformation of the expanded polyglutamine stretch leads to suppression of aggregate formation and cytotoxicity.

Journal Article Biochem Biophys Res Commun · May 14, 2004 The polyglutamine (polyQ) diseases are a class of inherited neurodegenerative diseases including Huntington's disease, caused by the expansion of a polyQ stretch within each disease protein. This expansion is thought to cause a conformational change in the ... Full text Link to item Cite

Effect of tissue transglutaminase on the solubility of proteins containing expanded polyglutamine repeats.

Journal Article J Neurochem · March 2004 The expansion of a polyglutamine (polyQ) domain in neuronal proteins is the molecular genetic cause of at least eight neurodegenerative diseases. Proteins with a polyQ domain that is greater than 40 Q (Q40) residues form insoluble intranuclear and cytoplas ... Full text Link to item Cite

APOE genotype-specific differences in human and mouse macrophage nitric oxide production.

Journal Article J Neuroimmunol · February 2004 Individuals expressing an APOE4 genotype demonstrate increased Alzheimer's disease (AD) neuropathology and a decreased onset age. The APOE4 gene may act by modulating the CNS immune response. Using human monocyte-derived macrophages (MDM), we show a signif ... Full text Link to item Cite

Cerebral embolization during cardiac surgery: impact of aortic atheroma burden.

Other Br J Anaesth · November 2003 BACKGROUND: Aortic atheromatous disease is known to be associated with an increased risk of perioperative stroke in the setting of cardiac surgery. In this study, we sought to determine the relationship between cerebral microemboli and aortic atheroma burd ... Full text Link to item Cite

ApoE genotype-specific inhibition of apoptosis.

Journal Article J Lipid Res · August 2003 Endothelial cell apoptosis can be initiated by withdrawing growth factors or serum, and is inhibited by HDL. Our results show that the total lipoprotein population from apolipoprotein E 4/4 (APOE4/4) sera is less anti-apoptotic than total lipoproteins from ... Full text Link to item Cite

Prevention of polyglutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila.

Journal Article Hum Mol Genet · June 1, 2003 Polyglutamine (polyQ) diseases are a growing class of inherited neurodegenerative diseases including Huntington's disease, which are caused by abnormal expansions of the polyQ stretch in each unrelated disease protein. The expanded polyQ stretch is thought ... Full text Link to item Cite

APOE genotype is a risk factor for neuropathy severity in diabetic patients.

Journal Article Neurology · March 25, 2003 This cross-sectional study tested the hypothesis that APOE genotype is a risk factor for diabetic neuropathy severity. A model with age, duration of diabetes, and APOE genotype was found to predict (p = 0.0083) severity on the Neuropathy Impairment Score i ... Full text Link to item Cite

In vitro effects of polyglutamine tracts on Ca2+-dependent depolarization of rat and human mitochondria: relevance to Huntington's disease.

Journal Article Arch Biochem Biophys · February 1, 2003 The mechanisms by which neurons die in CAG triplet repeat (polyglutamine) disorders, such as Huntington's disease, are uncertain; however, mitochondrial dysfunction and disordered calcium homeostasis have been implicated. We previously demonstrated abnorma ... Full text Link to item Cite

Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines.

Journal Article Nat Neurosci · August 2002 Huntington's disease (HD) is caused by an expansion of exonic CAG triplet repeats in the gene encoding huntingtin protein (Htt), but the mechanisms by which this mutant protein causes neurodegeneration remain unknown. Here we show that lymphoblast mitochon ... Full text Link to item Cite

Serum creatinine patterns in coronary bypass surgery patients with and without postoperative cognitive dysfunction.

Other Anesth Analg · July 2002 UNLABELLED: Renal dysfunction is common after coronary artery bypass graft (CABG) surgery. We have previously shown that CABG procedures complicated by stroke have a threefold greater peak serum creatinine level relative to uncomplicated surgery. However, ... Full text Link to item Cite

Expanded polyglutamine stretches form an 'aggresome'.

Journal Article Neurosci Lett · May 3, 2002 To understand the pathogenetic mechanisms underlying polyglutamine (polyQ) diseases, we investigated the mechanisms of the formation of aggregate bodies containing expanded polyQ stretches, focusing on dentatorubral-pallidoluysian atrophy (DRPLA). We demon ... Full text Link to item Cite

Molecular biology of apolipoprotein E.

Journal Article Curr Opin Lipidol · April 2002 Apolipoprotein E, first identified 26 years ago as a serum protein that mediates extracellular cholesterol transport, is now known to regulate multiple additional metabolic pathways. Several clinically important disorders of the vasculature and brain are d ... Full text Link to item Cite

The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery.

Other Anesth Analg · January 2002 UNLABELLED: Neurocognitive dysfunction is a common complication after cardiac surgery. We evaluated in this prospective study the effect of rewarming rate on neurocognitive outcome after hypothermic cardiopulmonary bypass (CPB). After IRB approval and info ... Full text Link to item Cite

Amino acid sequence requirements of peptides that inhibit polyglutamine-protein aggregation and cell death.

Journal Article Biochem Biophys Res Commun · November 2, 2001 Proteins with expanded polyglutamine domains cause eight inherited neurodegenerative diseases including Huntington's disease. In a previous paper, we identified peptides that inhibit polyglutamine protein aggregation and cell death and now describe the ami ... Full text Link to item Cite

Impairment of the blood-nerve and blood-brain barriers in apolipoprotein e knockout mice.

Journal Article Exp Neurol · May 2001 Apolipoprotein E (apoE) is well characterized as a plasma lipoprotein involved in lipid and cholesterol metabolism. Recent studies implicating apoE in Alzheimer's disease and successful recovery from neurological injury have stimulated much interest in the ... Full text Link to item Cite

Apolipoprotein E and Alzheimer's disease: signal transduction mechanisms.

Journal Article Biochem Soc Symp · 2001 The three common apolipoprotein E (ApoE) alleles differentially contribute to the risk of Alzheimer's disease (AD). While the APOE genotype alters susceptibility to disease expression, individuals with APOE epsilon 4 alleles have the highest risk of develo ... Full text Link to item Cite

Cdc2 phosphorylation of nucleolin demarcates mitotic stages and Alzheimer's disease pathology.

Journal Article Neurobiol Aging · 2001 Nucleolin is a major multifunctional nuclear phosphoprotein that is phosphorylated by Cdc2 kinase in mitosis and that participates in a number of cellular processes. The monoclonal antibody TG-3 generated against neurofibrillary tangles (NFT) found in Alzh ... Full text Link to item Cite

Apolipoprotein E and neuromuscular disease: a critical review of the literature.

Journal Article Arch Neurol · November 2000 Molecular mechanisms that alter the incidence and rate of neuromuscular disease progression are, in many cases, only partially understood. Several recent studies have asked whether apolipoprotein E (apoE for the protein, APOE for the gene) influences these ... Full text Link to item Cite

Preliminary report on the association of apolipoprotein E polymorphisms, with postoperative peak serum creatinine concentrations in cardiac surgical patients.

Journal Article Anesthesiology · August 2000 BACKGROUND: Renal dysfunction after cardiac surgery occurs in up to 8% of patients and is associated with major increases in morbidity, mortality, and cost. Genetic polymorphisms have been implicated as a factor in the progression of chronic renal disease, ... Full text Link to item Cite

The role of apolipoprotein E in Alzheimer's disease: pharmacogenomic target selection.

Journal Article Biochim Biophys Acta · July 26, 2000 The association of inheritance of different apolipoprotein E (APOE, gene; apoE, protein) alleles with the risk and rate of onset of Alzheimer's disease (AD) is now well established and widely confirmed. While there are now a collection of hypotheses concer ... Full text Link to item Cite

Inhibition of polyglutamine protein aggregation and cell death by novel peptides identified by phage display screening.

Journal Article J Biol Chem · April 7, 2000 Proteins with expanded polyglutamine domains cause eight inherited neurodegenerative diseases, including Huntington's, but the molecular mechanism(s) responsible for neuronal degeneration are not yet established. Expanded polyglutamine domain proteins poss ... Full text Link to item Cite

Apolipoprotein E and Alzheimer's disease.

Journal Article Ann N Y Acad Sci · 2000 The specific molecular pathway by which apolipoprotein E modifies the expression of Alzheimer's disease remains elusive. Isoform-specific interactions of apolipoprotein E with other molecules determine the outcome from other neurologic disorders and may pr ... Full text Link to item Cite

Pathogenesis of inclusion bodies in (CAG)n/Qn-expansion diseases with special reference to the role of tissue transglutaminase and to selective vulnerability.

Journal Article J Neurochem · March 1999 At least eight neurodegenerative diseases, including Huntington disease, are caused by expansions in (CAG)n repeats in the affected gene and by an increase in the size of the corresponding polyglutamine domain in the expressed protein. A hallmark of severa ... Full text Link to item Cite

Expanded polyglutamine domain proteins bind neurofilament and alter the neurofilament network.

Journal Article Exp Neurol · February 1999 Eight inherited neurodegenerative diseases are caused by genes with expanded CAG repeats coding for polyglutamine domains in the disease-producing proteins. The mechanism by which this expanded polyglutamine domain causes neurodegenerative disease is unkno ... Full text Link to item Cite

Generation of neuronal intranuclear inclusions by polyglutamine-GFP: analysis of inclusion clearance and toxicity as a function of polyglutamine length.

Journal Article J Neurosci · January 15, 1999 Recent evidence suggests that, in huntingtin and many other proteins, polyglutamine repeats are a toxic stimulus in neurodegenerative diseases. To investigate the mechanism by which these repeats may be toxic, we transfected primary rat cerebellar granule ... Full text Link to item Cite

Polyglutamine domain proteins with expanded repeats bind neurofilament, altering the neurofilament network.

Journal Article Ann N Y Acad Sci · 1999 Proteins with expanded polyglutamine (polyQ) repeats cause eight inherited neurodegenerative diseases. Nuclear and cytoplasmic polyQ protein is a common feature of these diseases, but its role in cell death remains debatable. Since the neuronal intermediat ... Full text Link to item Cite

Peripheral sensory nerve defects in apolipoprotein E knockout mice.

Journal Article Exp Neurol · September 1998 Apolipoprotein E (apoE), a plasma lipoprotein involved in lipid metabolism, is also proposed to have important functions within the central and peripheral nervous systems. To investigate the function of apoE in the peripheral nervous system, we examined th ... Full text Link to item Cite

Human apolipoprotein E accelerates microtubule polymerization in vitro.

Journal Article Neurosci Lett · April 3, 1998 Apolipoprotein E (apoE) is a 34-kDa protein implicated in Alzheimer's disease (AD) that has recently been identified in neuronal cytoplasm. In cultured neurons, the two major isoforms of apoE (E3 and E4) differentially affect neurite extension, microtubule ... Full text Link to item Cite

Novel large apolipoprotein E-containing lipoproteins of density 1.006-1.060 g/ml in human cerebrospinal fluid.

Journal Article J Neurochem · March 1998 Although the critical role of apolipoprotein E (apoE) allelic variation in Alzheimer's disease and in the outcome of CNS injury is now recognized, the functions of apoE in the CNS remain obscure, particularly with regard to lipid metabolism. We used densit ... Full text Link to item Cite

Glyceraldehyde 3-phosphate dehydrogenase abnormality in metabolically stressed Huntington disease fibroblasts.

Journal Article Dev Neurosci · 1998 Huntington disease (HD) fibroblasts subjected to stress exhibit an enzyme profile that is different from that exhibited by escapee (unaffected members of families with HD) or control fibroblasts. The specific activity of glyceraldehyde 3-phosphate dehydrog ... Full text Link to item Cite

Inhibition of α-ketoglutarate-and pyruvate dehydrogenase complexes in E. coli by a glutathione S-transferase containing a pathological length poly-Q domain: A possible role of energy deficit in neurological diseases associated with poly-Q expansions?

Journal Article Age (Omaha) · January 1998 At least seven adult-onset neurodegenerative diseases, including Huntington's disease (HD), are caused by genes containing expanded CAG triplets within their coding regions. The expanded CAG repeats give rise to extended stretches of polyglutamines (Qn) in ... Full text Link to item Cite

Nmr investigation of a microtubule binding region peptide from human tau (τ) protein

Journal Article Protein and Peptide Letters · December 1, 1997 Solution NMR studies of τD1, an 18-residue microtubule binding peptide from domain 1 of human tau protein, are reported. Using 2D 1H NMR (TOCSY, NOESY and ROESY) at 5 and 37°C, we assigned the resonances of almost all protons of τD1 at pH 4.2,5.8 and 7.3. ... Cite

Transglutaminase-catalyzed inactivation of glyceraldehyde 3-phosphate dehydrogenase and alpha-ketoglutarate dehydrogenase complex by polyglutamine domains of pathological length.

Journal Article Proc Natl Acad Sci U S A · November 11, 1997 Several adult-onset neurodegenerative diseases are caused by genes with expanded CAG triplet repeats within their coding regions and extended polyglutamine (Qn) domains within the expressed proteins. Generally, in clinically affected individuals n >/= 40. ... Full text Link to item Cite

Oligomerization of expanded-polyglutamine domain fluorescent fusion proteins in cultured mammalian cells.

Journal Article Biochem Biophys Res Commun · September 18, 1997 Six inherited neurologic diseases, including Huntington's disease, result from the expansion of a CAG domain of the disease genes to produce a domain of more than 40 glutamines in the expressed protein. The mechanism by which expansion of this polyglutamin ... Full text Link to item Cite

Preliminary report of a genetic basis for cognitive decline after cardiac operations. The Neurologic Outcome Research Group of the Duke Heart Center.

Other Ann Thorac Surg · September 1997 BACKGROUND: Changes in memory and cognition frequently follow cardiac operations. We hypothesized that patients with the apolipoprotein E-epsilon 4 allele are genetically predisposed to cognitive dysfunction after cardiac operations. METHODS: The apolipopr ... Full text Link to item Cite

Apolipoprotein E binds to and potentiates the biological activity of ciliary neurotrophic factor.

Journal Article J Neurosci · August 15, 1997 Expression of apolipoprotein E (apoE) and ciliary neurotrophic factor (CNTF), a pleiotropic neuron survival factor, increases in the CNS in response to injury. Although CNTF is believed to act as a survival factor after injury in the CNS, the functions of ... Full text Link to item Cite

Polyglutamine domains are substrates of tissue transglutaminase: does transglutaminase play a role in expanded CAG/poly-Q neurodegenerative diseases?

Journal Article J Neurochem · July 1997 Huntington's disease and six other neurodegenerative diseases are associated with abnormal gene products containing expanded polyglutamine (poly-Q; Qn) domains (n > or = 40). In the present work, we show that glutathione S-transferase (GST) fusion proteins ... Full text Link to item Cite

Toxicity of expanded polyglutamine-domain proteins in Escherichia coli.

Journal Article FEBS Lett · December 9, 1996 Five neurodegenerative diseases are caused by proteins with expanded polyglutamine domains. Toxicity of these proteins has been previously identified only in mammals, and no simple model systems are available. In this paper, we demonstrate in E. coli that ... Full text Link to item Cite

Specificity, sensitivity, and predictive value of apolipoprotein-E genotyping for sporadic Alzheimer's disease.

Journal Article Lancet · July 13, 1996 BACKGROUND: We aimed to determine the specificity, sensitivity, and predictive value of apolipoprotein E (APOE) genotyping in 67 consecutive patients with clinical diagnoses of sporadic Alzheimer's disease (AD) who underwent necropsy. METHODS: We studied p ... Full text Link to item Cite

Differential binding of apolipoprotein E isoforms to tau and other cytoskeletal proteins.

Journal Article Exp Neurol · April 1996 The apolipoprotein E4 (apoE4) gene dose is a major risk factor for late-onset and sporadic Alzheimer's disease with 50% of homozygous patients developing the disease by age 70. Previous studies have shown localization of apoE to the cytoplasm of certain ne ... Full text Link to item Cite

Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH.

Journal Article Nat Med · March 1996 At least five adult-onset neurodegenerative diseases, including Huntingtin disease (HD), and dentatorubral-pallidoluysian atrophy (DRPLA) are produced by genes containing a variably increased CAG repeat within the coding region. The size range of the repea ... Full text Link to item Cite

Crosslinking of apolipoprotein E by products of lipid peroxidation.

Journal Article J Neuropathol Exp Neurol · February 1996 Apolipoprotein E (APOE) genotype and advancing aging are interacting ri sk factors in the expression of late onset and sporadic Alzheimer's Disease (AD). We tested the hypothesis that 2 products of lipid peroxidation, malondialdehyde (MDA) and 4 hydroxy-2- ... Full text Link to item Cite

Morphological, biochemical, and genetic support for an apolipoprotein E effect on microtubular metabolism.

Journal Article Ann N Y Acad Sci · January 17, 1996 There are two distinct viewpoints on the association of the inheritance of apolipoprotein E (APOE) alleles and the age of onset distribution of Alzheimer's disease (AD): genetic and phenotypic expression. There have been multiple corroborations of the APOE ... Full text Link to item Cite

Apolipoprotein E and Alzheimer's disease.

Journal Article Annu Rev Neurosci · 1996 The apolipoprotein E locus (APOE) is associated with variations in the age of onset and risk of Alzheimer's disease. The APOE4 allele increases the probability of disease at an earlier age. In contrast, the APOE3 and APOE2 alleles decrease the probability ... Full text Link to item Cite

E-4-hydroxy-2-nonenal is cytotoxic and cross-links cytoskeletal proteins in P19 neuroglial cultures.

Journal Article Am J Pathol · January 1996 Lipid peroxidation increases with age in brain and is elevated further in Alzheimer's disease. E-4-hydroxy-2-nonenal and malondialdehyde are products of lipid peroxidation that can adduct and cross-link protein. Neurofibrillary tangles, a feature of Alzhei ... Link to item Cite

Interaction of apolipoprotein E with laminin increases neuronal adhesion and alters neurite morphology.

Journal Article Exp Neurol · December 1995 The extracellular matrix protein laminin profoundly affects neuronal adhesion, spreading, differentiation, and growth by binding integrin-type cell surface receptors. Laminin binds other basement membrane components, including heparan sulfate proteoglycans ... Full text Link to item Cite

Apolipoprotein E, survival in Alzheimer's disease patients, and the competing risks of death and Alzheimer's disease.

Journal Article Neurology · July 1995 The apolipoprotein E (APOE) epsilon 4 allele carries an increased risk of a patient developing Alzheimer's disease (AD) while the epsilon 2 allele carries a decreased risk. We compared survival from the onset of AD in subjects with different numbers of eps ... Full text Link to item Cite

ApoE3 binding to tau tandem repeat I is abolished by tau serine262 phosphorylation.

Journal Article Neurosci Lett · June 16, 1995 The risk of Alzheimer's disease is determined, in part, by inheritance of specific alleles of ApoE. Isoform specific interactions of ApoE have been shown with the microtubule-associated protein tau, which forms the neurofibrillary tangle in this disease. S ... Full text Link to item Cite

Apolipoprotein E and Alzheimer disease.

Journal Article Proc Natl Acad Sci U S A · May 23, 1995 Inheritance of specific apolipoprotein E (apoE) alleles determines, in large part, the risk and mean age of onset of late-onset familial and sporadic Alzheimer disease. The mechanism by which the apoE isoforms differentially contribute to disease expressio ... Full text Link to item Cite

Apolipoprotein E E4 allele and risk of dementia.

Journal Article JAMA · February 1, 1995 Link to item Cite

Apolipoprotein E in Creutzfeldt-Jacob disease.

Journal Article Lancet · January 7, 1995 Link to item Cite

Apolipoprotein E in Creutzfeldt-Jakob disease.

Journal Article Lancet · January 7, 1995 Link to item Cite

Isoform-specific interactions of apolipoprotein E with the microtubule-associated protein MAP2c: implications for Alzheimer's disease.

Journal Article Neurosci Lett · November 21, 1994 The apolipoprotein E type 4 allele is a susceptibility gene for late-onset Alzheimer's disease. Apolipoprotein E is found in neurons, some of which contain paired helical filaments made of the microtubule-associated protein tau. Previous studies have demon ... Full text Link to item Cite

Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease.

Journal Article Proc Natl Acad Sci U S A · November 8, 1994 The apolipoprotein E (apoE) type 4 allele (APOE4) is a susceptibility gene for late-onset familial and sporadic Alzheimer disease. ApoE is found in some neurofibrillary tangle-bearing neurons, one of the major pathologic hallmarks of the disease. Neurofibr ... Full text Link to item Cite

Apolipoprotein E is localized to the cytoplasm of human cortical neurons: a light and electron microscopic study.

Journal Article J Neuropathol Exp Neurol · September 1994 To clarify the localization of the glial protein apolipoprotein E (apoE) in human cortical neurons, we employed specific immunoelectron microscopy using a monoclonal antibody to human apoE in surgical specimens of temporal lobe. The specimens were rapidly ... Full text Link to item Cite

Transthyretin sequesters amyloid beta protein and prevents amyloid formation.

Journal Article Proc Natl Acad Sci U S A · August 30, 1994 The cardinal pathological features of Alzheimer disease are depositions of aggregated amyloid beta protein (A beta) in the brain and cerebrovasculature. However, the A beta is found in a soluble form in cerebrospinal fluid in healthy individuals and patien ... Full text Link to item Cite

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

Journal Article J Clin Invest · August 1994 Late-onset and sporadic Alzheimer's disease are associated with the apolipoprotein E (apoE) type 4 allele expressing the protein isoform apoE4. Apolipoprotein E binds avidly to beta amyloid (A beta) peptide, a major component of senile plaque of Alzheimer' ... Full text Link to item Cite

Apolipoprotein E is present in hippocampal neurons without neurofibrillary tangles in Alzheimer's disease and in age-matched controls.

Journal Article Exp Neurol · July 1994 Apolipoprotein E (apoE, protein; APOE, gene) is a susceptibility gene for late-onset familial and sporadic Alzheimer's disease (AD). To examine the role of apoE in the pathogenesis of AD, we used immunocytochemistry to compare apoE localization in the hipp ... Full text Link to item Cite

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

Journal Article Nat Genet · June 1994 Gene dosage of the apolipoprotein E (APOE) epsilon 4 allele is a major risk factor for familial Alzheimer disease (AD) of late onset (after age 60). Here we studied a large series of 115 AD case subjects and 243 controls as well as 150 affected and 197 una ... Full text Link to item Cite

The role of apolipoprotein E in the nervous system.

Journal Article Curr Opin Lipidol · April 1994 Human apolipoprotein (apo)E, an important component of plasma lipoprotein metabolism, was recently linked to Alzheimer's disease. Of the three common apoE alleles, epsilon 4 has emerged as a major risk factor. This review summarizes the data leading to thi ... Full text Link to item Cite

Attenuation of the neurotoxic effect of A beta amyloid peptide by apolipoprotein E.

Journal Article Biochem Biophys Res Commun · February 28, 1994 Alzheimer's disease patients have increased frequency of apolipoprotein E allele c4, suggesting apoE4 is a risk factor determining disease. ApoE binds A beta amyloid peptide with great avidity in vitro and in the neuritic plaque. Potentially, binding of A ... Full text Link to item Cite

Hypothesis: microtubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype.

Journal Article Exp Neurol · February 1994 A genetic classification of Alzheimer disease(s) (AD) is presented. We describe a potential metabolic process in individuals who inherit apolipoprotein E-epsilon 4 (APOE4, gene; apoE4, protein) alleles, leading to increased risk and earlier age of onset of ... Full text Link to item Cite

Complex genetic disease: can genetic strategies in Alzheimer's disease and new genetic mechanisms be applied to epilepsy?

Journal Article Epilepsia · 1994 Strategies used in molecular genetics have changed modern neurology. The gene or genes responsible for several major neurologic diseases have now been identified using "reverse" or positional genetics. Unexpected new genetic mechanisms have been discovered ... Full text Link to item Cite

Apolipoprotein E ε4

Journal Article Neurology · January 1, 1994 Full text Cite

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

Journal Article Proc Natl Acad Sci U S A · October 15, 1993 Amyloid beta-peptide (A beta) deposition in senile plaques and cerebral vessels is a neuropathological feature of Alzheimer disease (AD). We examined the possibility that commonly observed variability in A beta deposition in late-onset AD might be related ... Full text Link to item Cite

Sequestration of amyloid beta-peptide.

Journal Article Ann N Y Acad Sci · September 24, 1993 Amyloid beta-protein, or beta/A4, is a 4-kilodalton peptide that forms poorly soluble extracellular depositions of amyloid in brains and leptomeninges of patients with Alzheimer's disease (AD), Down's syndrome (DS), and hereditary cerebral hemorrhage with ... Full text Link to item Cite

Apolipoprotein E epsilon 4 allele distributions in late-onset Alzheimer's disease and in other amyloid-forming diseases.

Journal Article Lancet · September 18, 1993 The frequency of the allele for apolipoprotein E type 4 (epsilon 4) is increased in late-onset familial and sporadic Alzheimer's disease (AD). We have examined epsilon 4 frequencies in four distinct, normal, elderly control groups and, most importantly, in ... Full text Link to item Cite

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

Journal Article Proc Natl Acad Sci U S A · September 1, 1993 Apolipoprotein E (apoE), a plasma apolipoprotein that plays a central role in lipoprotein metabolism, is localized in the senile plaques, congophilic angiopathy, and neurofibrillary tangles of Alzheimer disease. Late-onset familial and sporadic Alzheimer d ... Full text Link to item Cite

Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.

Journal Article Science · August 13, 1993 The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with ... Full text Link to item Cite

Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease.

Journal Article Neurology · August 1993 Apolipoprotein E, type epsilon 4 allele (APOE epsilon 4), is associated with late-onset familial Alzheimer's disease (AD). There is high avidity and specific binding of amyloid beta-peptide with the protein ApoE. To test the hypothesis that late-onset fami ... Full text Link to item Cite

Avid binding of beta A amyloid peptide to its own precursor.

Journal Article Exp Neurol · August 1993 The senile plaque and congophilic angiopathy in brains of patients with Alzheimer's disease contain abnormal extracellular depositions. These depositions have very complex molecular structure, some elements of which have been identified. The most abundant ... Full text Link to item Cite

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

Journal Article Proc Natl Acad Sci U S A · March 1, 1993 Apolipoprotein E is immunochemically localized to the senile plaques, vascular amyloid, and neurofibrillary tangles of Alzheimer disease. In vitro, apolipoprotein E in cerebrospinal fluid binds to synthetic beta A4 peptide (the primary constituent of the s ... Full text Link to item Cite

Binding of IgG to amyloid beta A4 peptide via the heavy-chain hinge region with preservation of antigen binding.

Journal Article J Neuroimmunol · 1993 Amyloid beta A4 peptide is found in the extracellular region of the senile plaque and in the angiopathy of Alzheimer's disease. Several other proteins, including IgG, also reside in these abnormal structures. In an attempt to understand how these structure ... Full text Link to item Cite

Alzheimer's disease - reassessing the data

Journal Article Current Biology · January 1, 1992 Full text Cite

Cellular functions of metallo-endoproteinases.

Journal Article Biochim Biophys Acta · July 22, 1991 Full text Link to item Cite

Low yield in the diagnostic evaluation of transient ischemic attacks.

Journal Article Neurology · May 1990 Among 163 patients presenting with the clinical features of a TIA, extensive testing identified only 2 patients with nonatherosclerotic causes. We conclude that most patients with a TIA have atherosclerotic vascular disease and that screening tests for oth ... Full text Link to item Cite

Neuropathological and neuropsychological changes in Alzheimer's disease. Relationship of biologic markers to behavioral markers.

Journal Article Clin Geriatr Med · August 1989 Alzheimer's disease is the fourth most common cause of death in the United States, and is the leading cause of functional disability in the elderly. This article analyzes the pathologic validity of mental status tests and the biochemistry of Alzheimer's di ... Link to item Cite

Inhibitors of metalloendoproteases block spiculogenesis in sea urchin primary mesenchyme cells.

Journal Article Exp Cell Res · April 1989 Metalloendoproteases have been implicated in a variety of fusion processes including plasma membrane fusion and exocytosis. As a prerequisite to skeleton formation in the sea urchin embryo, primary mesenchyme cells undergo fusion via filopodia to form sync ... Full text Link to item Cite

Will neurotrophic agents be harmful in Alzheimer's disease?

Journal Article Neurobiol Aging · 1989 The thesis that neurotrophic therapy in Alzheimer's disease may exacerbate the pathological state merits careful experimental verification. We are concerned about prematurely dismissing an important avenue of potential therapy which would provide a trophic ... Full text Link to item Cite

Glutamate and dynorphin release from a subcellular fraction enriched in hippocampal mossy fiber synaptosomes.

Journal Article Brain Res Bull · September 1988 A procedure is described for the isolation of intact hippocampal mossy fiber synaptosomes. Electron microscopic examination revealed numerous synaptosomal profiles which are clearly of mossy fiber origin, indicated by their large size (2-6 micron diameter) ... Full text Link to item Cite

Evidence for involvement of metalloendoproteases in a step in sea urchin gamete fusion.

Journal Article J Cell Biol · August 1988 Membrane fusion events are required in three steps in sea urchin fertilization: the acrosome reaction in sperm, fusion of the plasma membrane of acrosome-reacted sperm with the plasma membrane of the egg, and exocytosis of the contents of the egg cortical ... Full text Link to item Cite

Molecular mechanisms of exocytosis: the adrenal chromaffin cell as a model system.

Journal Article Cell Mol Neurobiol · March 1988 1. The release of neurotransmitters, hormones, and enzymes involves exquisitely regulated events which ultimately result in the fusion of the secretory vesicle with the cell's plasma membrane, releasing the vesicle contents into the extracellular space. 2. ... Full text Link to item Cite

Specific inhibitors implicate a soluble metalloendoproteinase in exocytosis.

Journal Article Cell Mol Neurobiol · December 1987 1. Previous studies have demonstrated that exocytosis in adrenal chromaffin cells appears to require zinc-dependent endoproteinase activity. 2. Chromaffin cells have metal-dependent endoproteinases in both the plasma membrane and the soluble fraction of ho ... Full text Link to item Cite

The soluble metalloendoprotease required in myoblast fusion remains intracellular.

Journal Article Biochem Biophys Res Commun · August 31, 1987 The fusion of myoblasts to myotubes requires an endogenous soluble metalloendoprotease. To determine whether this protease is released by fusing myoblasts, or stays within the cell, we examined the effects of membrane-impermeant and a membrane-permeant met ... Full text Link to item Cite

Evidence for the involvement of metalloendoproteases in the acrosome reaction in sea urchin sperm.

Journal Article J Biol Chem · April 25, 1987 An essential initial step in fertilization in the sea urchin Strongylocentrotus purpuratus is an intracellular membrane fusion event in the sperm known as the acrosome reaction. This Ca2+-dependent, exocytotic process involves fusion of the membrane of the ... Link to item Cite

Requirement for metalloendoprotease in exocytosis: evidence in mast cells and adrenal chromaffin cells.

Journal Article Cell · March 1985 Exocytosis is initiated by the receptor-mediated influx of calcium that results in fusion of the secretory vesicle with the plasma membrane. We examined the possibility that calcium-dependent exocytosis in mast cells and adrenal chromaffin cells requires m ... Full text Link to item Cite

Inhibitors of metalloendoprotease activity prevent K+-stimulated neurotransmitter release from the retina of Xenopus laevis.

Journal Article J Neurosci · December 1984 Metalloendoprotease activity was identified in retinal homogenates using a synthetic fluorogenic metalloendoprotease substrate and specific metalloendoprotease inhibitors. The requirement of metalloendoprotease activity in neurotransmitter release was exam ... Full text Link to item Cite

Specific blockers of myoblast fusion inhibit a soluble and not the membrane-associated metalloendoprotease in myoblasts.

Journal Article J Biol Chem · May 10, 1984 We previously reported that the cell fusion that occurs during muscle development, when mononucleated myoblasts fuse to form multinucleated myotubes, requires endogenous metalloendoprotease activity at the time of fusion. We report here that myoblasts cont ... Link to item Cite

Protease inhibitors implicate metalloendoprotease in synaptic transmission at the mammalian neuromuscular junction.

Journal Article Proc Natl Acad Sci U S A · July 1983 Metalloendoproteases have been implicated in the calcium-dependent exocytosis of histamine from mast cells and in the calcium-dependent fusion of myoblasts. Because metalloendoproteases have also been identified in nervous tissue, we investigated the possi ... Full text Link to item Cite

Rat myoblast fusion requires metalloendoprotease activity.

Journal Article Cell · January 1983 The calcium-dependent fusion of cultured rat myoblasts to multinucleate myotubes appears to require the activity of a neutral metalloendoprotease at the time of fusion. Metalloendoprotease inhibitors and synthetic dipeptide substrates prevent myoblast fusi ... Full text Link to item Cite

Phospholipid methylation: a possible mechanism of signal transduction across biomembranes.

Journal Article Prog Clin Biol Res · 1981 The conversion of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) is catalyzed by two methyltransferases with S-adenosylmethionine as the methyl donor. PC formed by transmethylation is further metabolized by phospholipase A2. The synthesis and de ... Link to item Cite

Regulation of the beta-adrenergic receptor by methylation of membrane phospholipids.

Journal Article Adv Cyclic Nucleotide Res · 1981 Stimulation of the beta-adrenergic receptor increases the enzymatic methylation of membrane phospholipids. Increased synthesis of phosphatidyl-N-monomethylethanolamine by methyltransferase I increases fluidity and enhances the ability of the beta-adrenergi ... Link to item Cite

Modification of calmodulin function by enzymatic carboxyl methylation

Journal Article Nature · 1981 Calmodulin is a ubiquitous calcium-binding protein that regulates a variety of enzymes such as adenylate cyclase, cyclic nucleotide phosphodiesterase, ATPase and protein kinase. So far, no enzymatic modification of calmodulin has been shown to affect its f ... Full text Cite

Protein carboxyl-methylase modifies calmodulin function.

Journal Article Annals of the New York Academy of Sciences · 1980 Cite

Mepacrine blocks β-adrenergic agonist-induced desensitization in astrocytoma cells

Journal Article Proceedings of the National Academy of Sciences of the United States of America · 1980 Cite

Studies on benzodiazepine receptors.

Journal Article Advances in biochemical psychopharmacology · 1980 Cite

Phospholipid methylation unmasks cryptic beta-adrenergic receptors in rat reticulocytes.

Journal Article Science · June 15, 1979 The effect of phospholipid methylation on the number of beta-adrenergic receptor binding sites was examined in rat reticulocyte membranes. Stimulation of phosphatidylcholine synthesis by the introduction of the methyl donor S-adenosyl-L-methionine into ret ... Full text Link to item Cite

beta-Adrenergic receptor agonists increase phospholipid methylation, membrane fluidity, and beta-adrenergic receptor-adenylate cyclase coupling.

Journal Article Proc Natl Acad Sci U S A · January 1979 The beta-adrenergic agonist L-isoproterenol stimulated the enzymic synthesis of phosphatidyl-N-monomethylethanolamine and phosphatidylcholine in rat reticulocyte ghosts containing the methyl donor S-adenosyl-L-methionine. The stimulation was stereospecific ... Full text Link to item Cite

Beta adrenergic stimulation of protein carboxymethylation and amylase secretion in rat parotid gland.

Journal Article J Pharmacol Exp Ther · November 1978 Protein carboxymethylase (S-adenosyl-l-methionine:protein-O-methyltransferase, EC 2.1.1.24) transfers methyl groups from S-adenosylmethionine to protein carboxyl groups. This cytosolic enzyme is found in highest concentration in secretory tissue and methyl ... Link to item Cite

α Adrenergic receptors in rat parotid cells. I. Correlation of [3H] dihydroergocryptine binding and catecholamine stimulated potassium efflux

Journal Article Journal of Biological Chemistry · December 1, 1977 α-Adrenergic stimulation of parotid acinar cells elicits a release of intracellular K+. The binding of [3H]dihydroergocryptine was used to characterize the α-adrenergic receptor binding sites in both parotid membranes and dissociated parotid acinar cells. ... Cite

α Adrenergic receptors in rat parotid cells. II. Desensitization of receptor binding sites and potassium release

Journal Article Journal of Biological Chemistry · December 1, 1977 Preincubation of dissociated rat parotid acinar cells with the α-adrenergic agonist epinephrine produced a time- and concentration-dependent decrement in the α-adrenergic response of the cells, K+ release. This receptor desensitization by epinephrine was s ... Cite

[3H]dihydroergocryptine binding in rat brain.

Journal Article Brain Res · August 26, 1977 [3H]dihydroergocryptine (DHE) appears to bind to alpha-adrenergic receptor sites in rabbit uterine membranes. We have characterized the binding of [3H]DHE to membranes prepared from rat cerebral cortex. alpha-Adrenergic agents were less potent and dopamine ... Full text Link to item Cite