Selkoe DJ. Alzheimer’s disease results from the cerebral accumulation and cytotoxicity of amyloid ß-protein. J Alzheimers Dis. 2001;3(1):75–80.
Article
PubMed
CAS
Google Scholar
Dawkins E, Small DH. Insights into the physiological function of the β-amyloid precursor protein: beyond Alzheimer’s disease. J Neurochem. 2014;129(5):756–69.
Article
PubMed
PubMed Central
CAS
Google Scholar
Giuffrida ML, Caraci F, Pignataro B, Cataldo S, Bona PD, Bruno V, et al. β-Amyloid monomers are neuroprotective. J Neurosci. 2009;29(34):10582–7.
Article
PubMed
PubMed Central
CAS
Google Scholar
Giuffrida ML, Tomasello MF, Pandini G, Caraci F, Battaglia G, Busceti C, et al. Monomeric ß-amyloid interacts with type-1 insulin-like growth factor receptors to provide energy supply to neurons. Front Cell Neurosci. 2015;9:297.
Article
PubMed
PubMed Central
Google Scholar
Grimm MOW, Grimm HS, Hartmann T. Amyloid beta as a regulator of lipid homeostasis. Trends Mol Med. 2007;13(8):337–44.
Article
PubMed
CAS
Google Scholar
Zimbone S, Monaco I, Gianì F, Pandini G, Copani AG, Giuffrida ML, et al. Amyloid Beta monomers regulate cyclic adenosine monophosphate response element binding protein functions by activating type-1 insulin-like growth factor receptors in neuronal cells. Aging Cell. 2018;17(1):e12684.
Article
PubMed
Google Scholar
Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science. 1992;256(5054):184–5.
Article
PubMed
CAS
Google Scholar
Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science. 2002;297(5580):353–6.
Article
PubMed
CAS
Google Scholar
De S, Wirthensohn DC, Flagmeier P, Hughes C, Aprile FA, Ruggeri FS, et al. Different soluble aggregates of Aβ42 can give rise to cellular toxicity through different mechanisms. Nat Commun. 2019;10(1):1541.
Article
PubMed
PubMed Central
Google Scholar
Esparza TJ, Wildburger NC, Jiang H, Gangolli M, Cairns NJ, Bateman RJ, et al. Soluble amyloid-beta aggregates from human Alzheimer’s disease brains. Sci Rep. 2016;5(6):38187.
Article
Google Scholar
He Y, Zheng MM, Ma Y, Han XJ, Ma XQ, Qu CQ, et al. Soluble oligomers and fibrillar species of amyloid β-peptide differentially affect cognitive functions and hippocampal inflammatory response. Biochem Biophys Res Commun. 2012;429(3–4):125–30.
Article
PubMed
CAS
Google Scholar
Sehlin D, Englund H, Simu B, Karlsson M, Ingelsson M, Nikolajeff F, et al. Large aggregates are the major soluble Aβ species in AD brain fractionated with density gradient ultracentrifugation. PLoS One. 2012;7(2):e32014.
Article
PubMed
PubMed Central
CAS
Google Scholar
Sideris DI, Danial JSH, Emin D, Ruggeri FS, Xia Z, Zhang YP, et al. Soluble amyloid beta-containing aggregates are present throughout the brain at early stages of Alzheimer’s disease. Brain Commun. 2021;3(3):fcab147.
Article
PubMed
PubMed Central
Google Scholar
Spencer B, Rockenstein E, Crews L, Marr R, Masliah E. Novel strategies for Alzheimer’s disease treatment. Expert Opin Biol Ther. 2007;7(12):1853–67.
Article
PubMed
CAS
Google Scholar
Tolar M, Abushakra S, Hey JA, Porsteinsson A, Sabbagh M. Aducanumab, gantenerumab, BAN2401, and ALZ-801—the first wave of amyloid-targeting drugs for Alzheimer’s disease with potential for near term approval. Alzheimers Res Ther. 2020;12(1):95.
Article
PubMed
PubMed Central
CAS
Google Scholar
Campos CR, Kemble AM, Niewoehner J, Freskgård PO, Urich E. Brain shuttle neprilysin reduces central amyloid-β levels. PLoS One. 2020;15(3):e0229850.
Article
PubMed
PubMed Central
CAS
Google Scholar
Rofo F, Ugur Yilmaz C, Metzendorf N, Gustavsson T, Beretta C, Erlandsson A, et al. Enhanced neprilysin-mediated degradation of hippocampal Aβ42 with a somatostatin peptide that enters the brain. Theranostics. 2021;11(2):789–804.
Article
PubMed
PubMed Central
CAS
Google Scholar
Sikanyika NL, Parkington HC, Smith AI, Kuruppu S. Powering amyloid beta degrading enzymes: a possible therapy for Alzheimer’s disease. Neurochem Res. 2019;44(6):1289–96.
Article
PubMed
CAS
Google Scholar
Miners JS, Barua N, Kehoe PG, Gill S, Love S. Aβ-degrading enzymes: potential for treatment of Alzheimer disease. J Neuropathol Exp Neurol. 2011;70(11):944–59.
Article
PubMed
CAS
Google Scholar
Devault A, Lazure C, Nault C, Le Moual H, Seidah NG, Chrétien M, et al. Amino acid sequence of rabbit kidney neutral endopeptidase 24.11 (enkephalinase) deduced from a complementary DNA. EMBO J. 1987;6(5):1317–22.
Article
PubMed
PubMed Central
CAS
Google Scholar
Kerr MA, Kenny AJ. The purification and specificity of a neutral endopeptidase from rabbit kidney brush border. Biochem J. 1974;137(3):477–88.
Article
PubMed
PubMed Central
CAS
Google Scholar
Iwata N, Sekiguchi M, Hattori Y, Takahashi A, Asai M, Ji B, et al. Global brain delivery of neprilysin gene by intravascular administration of AAV vector in mice. Sci Rep. 2013;3(1):1472.
Article
PubMed
PubMed Central
Google Scholar
Yasojima K, Akiyama H, McGeer EG, McGeer PL. Reduced neprilysin in high plaque areas of Alzheimer brain: a possible relationship to deficient degradation of β-amyloid peptide. Neurosci Lett. 2001;297(2):97–100.
Article
PubMed
CAS
Google Scholar
Wang S, Wang R, Chen L, Bennett DA, Dickson DW, Wang DS. Expression and functional profiling of neprilysin, insulin degrading enzyme and endothelin converting enzyme in prospectively studied elderly and Alzheimer’s brain. J Neurochem. 2010;115(1):47–57.
Article
PubMed
PubMed Central
CAS
Google Scholar
Kuruppu S, Rajapakse NW, Minond D, Smith AI. Production of soluble Neprilysin by endothelial cells. Biochem Biophys Res Commun. 2014;446(2):423–7.
Article
PubMed
CAS
Google Scholar
Howell S, Nalbantoglu J, Crine P. Neutral endopeptidase can hydrolyze beta-amyloid(1–40) but shows no effect on beta-amyloid precursor protein metabolism. Peptides. 1995;16(4):647–52.
Article
PubMed
CAS
Google Scholar
Iwata N, Tsubuki S, Takaki Y, Shirotani K, Lu B, Gerard NP, et al. Metabolic regulation of brain Aβ by neprilysin. Science. 2001;292(5521):1550–2.
Article
PubMed
CAS
Google Scholar
Iwata N, Takaki Y, Fukami S, Tsubuki S, Saido TC. Region-specific reduction of Aβ-degrading endopeptidase, neprilysin, in mouse hippocampus upon aging. J Neurosci Res. 2002;70(3):493–500.
Article
PubMed
CAS
Google Scholar
Takaki Y, Iwata N, Tsubuki S, Taniguchi S, Toyoshima S, Lu B, et al. Biochemical identification of the neutral endopeptidase family member responsible for the catabolism of amyloid beta peptide in the brain. J Biochem (Tokyo). 2000;128(6):897–902.
Article
PubMed
CAS
Google Scholar
Madani R, Poirier R, Wolfer DP, Welzl H, Groscurth P, Lipp HP, et al. Lack of neprilysin suffices to generate murine amyloid-like deposits in the brain and behavioral deficit in vivo. J Neurosci Res. 2006;84(8):1871–8.
Article
PubMed
CAS
Google Scholar
Mouri A, Zou LB, Iwata N, Saido TC, Wang D, Wang MW, et al. Inhibition of neprilysin by thiorphan (i.c.v.) causes an accumulation of amyloid β and impairment of learning and memory. Behav Brain Res. 2006;168(1):83–91.
Article
PubMed
CAS
Google Scholar
Newell AJ, Sue LI, Scott S, Rauschkolb PK, Walker DG, Potter PE, et al. Thiorphan-induced neprilysin inhibition raises amyloid beta levels in rabbit cortex and cerebrospinal fluid. Neurosci Lett. 2003;350(3):178–80.
Article
PubMed
CAS
Google Scholar
Leissring MA, Farris W, Chang AY, Walsh DM, Wu X, Sun X, et al. Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron. 2003;40(6):1087–93.
Article
PubMed
CAS
Google Scholar
Marr RA, Rockenstein E, Mukherjee A, Kindy MS, Hersh LB, Gage FH, et al. Neprilysin gene transfer reduces human amyloid pathology in transgenic mice. J Neurosci Off J Soc Neurosci. 2003;23(6):1992–6.
Article
CAS
Google Scholar
Oh JH, Choi S, Shin J, Park JS. Protective effect of recombinant soluble neprilysin against β-amyloid induced neurotoxicity. Biochem Biophys Res Commun. 2016;477(4):614–9.
Article
PubMed
CAS
Google Scholar
Park MH, Lee JK, Choi S, Ahn J, Jin HK, Park JS, et al. Recombinant soluble neprilysin reduces amyloid-beta accumulation and improves memory impairment in Alzheimer’s disease mice. Brain Res. 2013;5(1529):113–24.
Article
Google Scholar
Fang XT, Hultqvist G, Meier SR, Antoni G, Sehlin D, Syvänen S. High detection sensitivity with antibody-based PET radioligand for amyloid beta in brain. Neuroimage. 2019;01(184):881–8.
Article
Google Scholar
Hultqvist G, Syvänen S, Fang XT, Lannfelt L, Sehlin D. Bivalent brain shuttle increases antibody uptake by monovalent binding to the transferrin receptor. Theranostics. 2017;7(2):308–18.
Article
PubMed
PubMed Central
CAS
Google Scholar
Syvänen S, Hultqvist G, Gustavsson T, Gumucio A, Laudon H, Söderberg L, et al. Efficient clearance of Aβ protofibrils in AβPP-transgenic mice treated with a brain-penetrating bifunctional antibody. Alzheimers Res Ther. 2018;10(1):49.
Article
PubMed
PubMed Central
Google Scholar
Gustafsson S, Gustavsson T, Roshanbin S, Hultqvist G, Hammarlund-Udenaes M, Sehlin D, et al. Blood-brain barrier integrity in a mouse model of Alzheimer’s disease with or without acute 3D6 immunotherapy. Neuropharmacology. 2018;1(143):1–9.
Article
Google Scholar
Gustavsson T, Syvänen S, O’Callaghan P, Sehlin D. SPECT imaging of distribution and retention of a brain-penetrating bispecific amyloid-β antibody in a mouse model of Alzheimer’s disease. Transl Neurodegener. 2020;9(1):37.
Article
PubMed
PubMed Central
CAS
Google Scholar
Fang XT, Hultqvist G, Meier SR, Antoni G, Sehlin D, Syvänen S. High detection sensitivity with antibody-based PET radioligand for amyloid beta in brain. Neuroimage. 2019;1(184):881–8.
Article
Google Scholar
D’Elia E, Iacovoni A, Vaduganathan M, Lorini FL, Perlini S, Senni M. Neprilysin inhibition in heart failure: mechanisms and substrates beyond modulating natriuretic peptides. Eur J Heart Fail. 2017;19(6):710–7.
Article
PubMed
Google Scholar
Webster CI, Burrell M, Olsson LL, Fowler SB, Digby S, Sandercock A, et al. Engineering neprilysin activity and specificity to create a novel therapeutic for Alzheimer’s disease. PLoS One. 2014;9(8):e104001.
Article
PubMed
PubMed Central
Google Scholar
Lord A, Kalimo H, Eckman C, Zhang XQ, Lannfelt L, Nilsson LNG. The Arctic Alzheimer mutation facilitates early intraneuronal Abeta aggregation and senile plaque formation in transgenic mice. Neurobiol Aging. 2006;27(1):67–77.
Article
PubMed
CAS
Google Scholar
Nilsberth C, Westlind-Danielsson A, Eckman CB, Condron MM, Axelman K, Forsell C, et al. The ‘Arctic’ APP mutation (E693G) causes Alzheimer’s disease by enhanced Aβ protofibril formation. Nat Neurosci. 2001;4(9):887–93.
Article
PubMed
CAS
Google Scholar
Pope D, Madura JD, Cascio M. β-Amyloid and neprilysin computational studies identify critical residues implicated in binding specificity. J Chem Inf Model. 2014;54(4):1157–65.
Article
PubMed
CAS
Google Scholar
Fang XT, Sehlin D, Lannfelt L, Syvänen S, Hultqvist G. Efficient and inexpensive transient expression of multispecific multivalent antibodies in Expi293 cells. Biol Proced Online. 2017;19:11.
Article
PubMed
PubMed Central
Google Scholar
Rofo F, Buijs J, Falk R, Honek K, Lannfelt L, Lilja AM, et al. Novel multivalent design of a monoclonal antibody improves binding strength to soluble aggregates of amyloid beta. Transl Neurodegener. 2021;10(1):38.
Article
PubMed
PubMed Central
CAS
Google Scholar
Englund H, Sehlin D, Johansson AS, Nilsson LNG, Gellerfors P, Paulie S, et al. Sensitive ELISA detection of amyloid-beta protofibrils in biological samples. J Neurochem. 2007;103(1):334–45.
PubMed
CAS
Google Scholar
Greenwood F, Hunter W, Glover J. The preparation of 131 I-labelled human growth hormone of high specific radioactivity. Biochem J. 1963;89(1):114–23.
Article
PubMed
PubMed Central
CAS
Google Scholar
Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9(7):671–5.
Article
PubMed
PubMed Central
CAS
Google Scholar
Spencer B, Marr RA, Gindi R, Potkar R, Michael S, Adame A, et al. Peripheral delivery of a CNS targeted, metalo-protease reduces aβ toxicity in a mouse model of Alzheimer’s disease. PLoS One. 2011;6(1):e16575.
Article
PubMed
PubMed Central
CAS
Google Scholar
Lord A, Englund H, Söderberg L, Tucker S, Clausen F, Hillered L, et al. Amyloid-β protofibril levels correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice. FEBS J. 2009;276(4):995–1006.
Article
PubMed
PubMed Central
CAS
Google Scholar
Faresjö R, Bonvicini G, Fang XT, Aguilar X, Sehlin D, Syvänen S. Brain pharmacokinetics of two BBB penetrating bispecific antibodies of different size. Fluids Barriers CNS. 2021;18(1):26.
Article
PubMed
PubMed Central
Google Scholar
Morrison J, Metzendorf N, Rofo F, Petrovic A, Hultqvist G. A single chain fragment constant (scFc) design enables easy production of a monovalent BBB transporter and provides an improved brain uptake at elevated doses. Submitted. 2022.
Jin M, O’Nuallain B, Hong W, Boyd J, Lagomarsino VN, O’Malley TT, et al. An in vitro paradigm to assess potential anti-Aβ antibodies for Alzheimer’s disease. Nat Commun. 2018;9(1):2676.
Article
PubMed
PubMed Central
Google Scholar
Kanemitsu H, Tomiyama T, Mori H. Human neprilysin is capable of degrading amyloid β peptide not only in the monomeric form but also the pathological oligomeric form. Neurosci Lett. 2003;350(2):113–6.
Article
PubMed
CAS
Google Scholar
Crespi GAN, Hermans SJ, Parker MW, Miles LA. Molecular basis for mid-region amyloid-β capture by leading Alzheimer’s disease immunotherapies. Sci Rep. 2015;5(1):9649.
Article
PubMed
PubMed Central
CAS
Google Scholar
Hafez D, Huang JY, Huynh AM, Valtierra S, Rockenstein E, Bruno AM, et al. Neprilysin-2 is an important β-amyloid degrading enzyme. Am J Pathol. 2011;178(1):306–12.
Article
PubMed
PubMed Central
CAS
Google Scholar
Rofo F, Sandbaumhüter FA, Chourlia A, Metzendorf NG, Morrison JI, Syvänen S, et al. Wide-ranging effects on the brain proteome in a transgenic mouse model of Alzheimer’s disease following treatment with a brain-targeting somatostatin peptide. ACS Chem Neurosci. 2021;12(13):2529–41.
Article
PubMed
CAS
Google Scholar
Sato K, Tanabe C, Yonemura Y, Watahiki H, Zhao Y, Yagishita S, et al. Localization of mature neprilysin in lipid rafts. J Neurosci Res. 2012;90(4):870–7.
Article
PubMed
CAS
Google Scholar
Leissring MA, Lu A, Condron MM, Teplow DB, Stein RL, Farris W, et al. Kinetics of amyloid β-protein degradation determined by novel fluorescence- and fluorescence polarization-based assays *. J Biol Chem. 2003;278(39):37314–20.
Article
PubMed
CAS
Google Scholar
Shirotani K, Tsubuki S, Iwata N, Takaki Y, Harigaya W, Maruyama K, et al. Neprilysin degrades both amyloid β peptides 1–40 and 1–42 most rapidly and efficiently among thiorphan- and phosphoramidon-sensitive endopeptidases *. J Biol Chem. 2001;276(24):21895–901.
Article
PubMed
CAS
Google Scholar
Rosa A de la, Metzendorf NG, Morrison JI, Faresjö R, Rofo F, Petrovic A, et al. Introducing or removing heparan sulfate binding sites does not alter brain uptake of the blood-brain barrier shuttle scFv8D3. In Review; 2022 Oct [cited 25 Oct 2022]. Available from: https://www.researchsquare.com/article/rs-2166577/v1
Dempsey EC, Wick MJ, Karoor V, Barr EJ, Tallman DW, Wehling CA, et al. Neprilysin null mice develop exaggerated pulmonary vascular remodeling in response to chronic hypoxia. Am J Pathol. 2009;174(3):782–96.
Article
PubMed
PubMed Central
CAS
Google Scholar
van der Velden VH, Hulsmann AR. Peptidases: structure, function and modulation of peptide-mediated effects in the human lung. Clin Exp Allergy J Br Soc Allergy Clin Immunol. 1999;29(4):445–56.
Article
Google Scholar
Henderson SJ, Andersson C, Narwal R, Janson J, Goldschmidt TJ, Appelkvist P, et al. Sustained peripheral depletion of amyloid-β with a novel form of neprilysin does not affect central levels of amyloid-β. Brain. 2014;137(2):553–64.
Article
PubMed
Google Scholar
Walker JR, Pacoma R, Watson J, Ou W, Alves J, Mason DE, et al. Enhanced proteolytic clearance of plasma Aβ by peripherally administered neprilysin does not result in reduced levels of brain Aβ in mice. J Neurosci. 2013;33(6):2457–64.
Article
PubMed
PubMed Central
CAS
Google Scholar
Tsubuki S, Takaki Y, Saido TC. Dutch, Flemish, Italian, and Arctic mutations of APP and resistance of Abeta to physiologically relevant proteolytic degradation. Lancet Lond Engl. 2003;361(9373):1957–8.
Article
CAS
Google Scholar