Sustained peripheral depletion of amyloid-β with a novel form of neprilysin does not affect central levels of amyloid-β

Lowering levels of peripheral amyloid-β has been proposed as a strategy to reduce plaques in patients with Alzheimer’s disease. Henderson et al. test a modified version of the amyloid-degrading enzyme neprilysin in rats, monkeys and Tg2576 mice. Levels of amyloid-β were reduced in the bloodstream, but not in the CNS.

[1]  Jennifer L. Harris,et al.  Enhanced Proteolytic Clearance of Plasma Aβ by Peripherally Administered Neprilysin Does Not Result in Reduced Levels of Brain Aβ in Mice , 2013, The Journal of Neuroscience.

[2]  Britt-Marie Swahn,et al.  Discovery of AZD3839, a Potent and Selective BACE1 Inhibitor Clinical Candidate for the Treatment of Alzheimer Disease* , 2012, The Journal of Biological Chemistry.

[3]  M. Pangalos,et al.  Treatment strategies targeting amyloid β-protein. , 2012, Cold Spring Harbor perspectives in medicine.

[4]  N. Belyaev,et al.  Are amyloid‐degrading enzymes viable therapeutic targets in Alzheimer’s disease? , 2012, Journal of neurochemistry.

[5]  B. Strooper,et al.  The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics , 2011, Nature Reviews Drug Discovery.

[6]  O. Arancio,et al.  APP heterozygosity averts memory deficit in knockin mice expressing the Danish dementia BRI2 mutant , 2011, The EMBO journal.

[7]  D. H. Lee,et al.  Sink Hypothesis and Therapeutic Strategies for Attenuating Aβ Levels , 2011, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[8]  E. Masliah,et al.  Peripheral Delivery of a CNS Targeted, Metalo-Protease Reduces Aβ Toxicity in a Mouse Model of Alzheimer's Disease , 2011, PloS one.

[9]  J. Morris,et al.  Decreased Clearance of CNS β-Amyloid in Alzheimer’s Disease , 2010, Science.

[10]  T. Iwatsubo,et al.  A Noncompetitive BACE1 Inhibitor TAK-070 Ameliorates Aβ Pathology and Behavioral Deficits in a Mouse Model of Alzheimer's Disease , 2010, The Journal of Neuroscience.

[11]  J. Pons,et al.  Suppression of Amyloid Deposition Leads to Long-Term Reductions in Alzheimer's Pathologies in Tg2576 Mice , 2009, The Journal of Neuroscience.

[12]  I. Verma,et al.  Neprilysin: an enzyme candidate to slow the progression of Alzheimer's disease. , 2008, The American journal of pathology.

[13]  A. Goate,et al.  Clearance of amyloid-β by circulating lipoprotein receptors , 2007, Nature Medicine.

[14]  D. Selkoe,et al.  Reducing Amyloid Plaque Burden via Ex Vivo Gene Delivery of an Aβ-Degrading Protease: A Novel Therapeutic Approach to Alzheimer Disease , 2007, PLoS medicine.

[15]  J. Glorioso,et al.  Herpes simplex virus RNAi and neprilysin gene transfer vectors reduce accumulation of Alzheimer's disease-related amyloid-β peptide in vivo , 2006, Gene Therapy.

[16]  D. Holtzman,et al.  IgG-Assisted Age-Dependent Clearance of Alzheimer's Amyloid β Peptide by the Blood–Brain Barrier Neonatal Fc Receptor , 2005, The Journal of Neuroscience.

[17]  T. Golde,et al.  Anti-Aβ42– and anti-Aβ40–specific mAbs attenuate amyloid deposition in an Alzheimer disease mouse model , 2005 .

[18]  T. Comery,et al.  Acute γ-Secretase Inhibition Improves Contextual Fear Conditioning in the Tg2576 Mouse Model of Alzheimer's Disease , 2005, The Journal of Neuroscience.

[19]  R. Deane,et al.  RAGE (Yin) Versus LRP (Yang) Balance Regulates Alzheimer Amyloid &bgr;-Peptide Clearance Through Transport Across the Blood–Brain Barrier , 2004, Stroke.

[20]  D. Wilcock,et al.  Passive Amyloid Immunotherapy Clears Amyloid and Transiently Activates Microglia in a Transgenic Mouse Model of Amyloid Deposition , 2004, The Journal of Neuroscience.

[21]  H. Mizukami,et al.  Presynaptic Localization of Neprilysin Contributes to Efficient Clearance of Amyloid-β Peptide in Mouse Brain , 2004, The Journal of Neuroscience.

[22]  D. Selkoe,et al.  Enhanced Proteolysis of β-Amyloid in APP Transgenic Mice Prevents Plaque Formation, Secondary Pathology, and Premature Death , 2003, Neuron.

[23]  D. Selkoe,et al.  Kinetics of Amyloid β-Protein Degradation Determined by Novel Fluorescence- and Fluorescence Polarization-based Assays* , 2003, Journal of Biological Chemistry.

[24]  Ann Marie Schmidt,et al.  RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain , 2003, Nature Medicine.

[25]  F. Gage,et al.  Neprilysin Gene Transfer Reduces Human Amyloid Pathology in Transgenic Mice , 2003, The Journal of Neuroscience.

[26]  L. Hersh Peptidases, Proteases and Amyloid β-Peptide Catabolism , 2003 .

[27]  W. Pardridge,et al.  Expression of the neonatal Fc receptor (FcRn) at the blood–brain barrier , 2002, Journal of neurochemistry.

[28]  David J. Cummins,et al.  Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[29]  T. Iwatsubo,et al.  Neprilysin Degrades Both Amyloid β Peptides 1–40 and 1–42 Most Rapidly and Efficiently among Thiorphan- and Phosphoramidon-sensitive Endopeptidases* , 2001, The Journal of Biological Chemistry.

[30]  T. Saido,et al.  Metabolic Regulation of Brain Aβ by Neprilysin , 2001, Science.

[31]  F. Bian,et al.  Augmented senile plaque load in aged female beta-amyloid precursor protein-transgenic mice. , 2001, The American journal of pathology.

[32]  W. Pardridge,et al.  Mediated efflux of IgG molecules from brain to blood across the blood–brain barrier , 2001, Journal of Neuroimmunology.

[33]  D. Coates,et al.  The neprilysin (NEP) family of zinc metalloendopeptidases: Genomics and function , 2001, BioEssays : news and reviews in molecular, cellular and developmental biology.

[34]  D. Holtzman,et al.  Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. , 2000, The Journal of clinical investigation.

[35]  T. Saido,et al.  Biochemical identification of the neutral endopeptidase family member responsible for the catabolism of amyloid beta peptide in the brain. , 2000, Journal of biochemistry.

[36]  R. Motter,et al.  Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease , 2000, Nature Medicine.

[37]  T. Saido,et al.  Reply to: 'Clearance of amyloid β-peptide from brain: transport or metabolism?' , 2000, Nature Medicine.

[38]  T. Saido,et al.  Identification of the major Aβ1–42-degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition , 2000, Nature Medicine.

[39]  S. Younkin,et al.  Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice , 1996, Science.

[40]  S. Howell,et al.  Neutral endopeptidase can hydrolyze β-amyloid(1–40) but shows no effect on β-amyloid precursor protein metabolism , 1995, Peptides.

[41]  M. Fournié-Zaluski,et al.  Neutral endopeptidase 24.11: structure, inhibition, and experimental and clinical pharmacology. , 1993, Pharmacological reviews.

[42]  J. Hardy,et al.  Alzheimer's disease: the amyloid cascade hypothesis. , 1992, Science.

[43]  S. Love,et al.  Convection-enhanced delivery of neprilysin: a novel amyloid-β-degrading therapeutic strategy. , 2012, Journal of Alzheimer's disease : JAD.

[44]  J. Hardy,et al.  The Amyloid Hypothesis of Alzheimer ’ s Disease : Progress and Problems on the Road to Therapeutics , 2009 .

[45]  A. Goate,et al.  Clearance of amyloid-beta by circulating lipoprotein receptors. , 2007, Nature medicine.

[46]  J. Glorioso,et al.  Herpes simplex virus RNAi and neprilysin gene transfer vectors reduce accumulation of Alzheimer's disease-related amyloid-beta peptide in vivo. , 2006, Gene therapy.

[47]  T. Golde,et al.  Anti-Abeta42- and anti-Abeta40-specific mAbs attenuate amyloid deposition in an Alzheimer disease mouse model. , 2006, The Journal of clinical investigation.

[48]  L. Hersh Peptidases, proteases and amyloid beta-peptide catabolism. , 2003, Current pharmaceutical design.

[49]  T. Saido,et al.  Metabolic regulation of brain Abeta by neprilysin. , 2001, Science.

[50]  S. Howell,et al.  Neutral endopeptidase can hydrolyze beta-amyloid(1-40) but shows no effect on beta-amyloid precursor protein metabolism. , 1995, Peptides.