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The Biological Function of Amyloid β/A4 Protein Precursor

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Amyloid Protein Precursor in Development, Aging and Alzheimer’s Disease

Part of the book series: Research and Perspectives in Alzheimer’s Disease ((ALZHEIMER))

Abstract

Amyloid β/A4 protein precursor (APP) is secreted into medium by most cultured cells and can function as an autocrine factor. To study the biological function of secreted forms of APP (sAPP) on neurons, we used a clonal CNS neuronal line B103 which synthesizes no detectable levels of APP. When B103 cells were plated at a low density in a defined serum-free medium, neurite outgrowth was promoted by the conditioned medium of APP-695 over-producing cells and by the bacteria-produced sAPP-695 (named KB75). A series of peptides having sequences between Ala-319 and Met-335 of APP-695 also stimulated neurite outgrowth of B103 cells. The sequence of five amino acids, RERMS (APP 328–332) within this stretch of sequence, was the shortest active peptide. Binding assay using 125l-labeled APP 17-mer peptide corresponding to Ala-319 to Met-335 of APP-695 as a ligand demonstrated specific and saturable cell-surface binding sites which are extractable with detergent. These data indicate that sAPP induces neurite extension through a cell surface binding and that the RERMS domain represents the active site responsible for this function. The RERMS-containing APP peptide also exhibited neuronal survival activity on rat primary cortical neuronal culture. In addition, the infusion of the trophic APP peptide into rat brain ventricles increased the synaptic density in the frontoparietal cortex and enhanced the memory retention. These results firmly establish the neurotrophic properties of sAPP and raise the possibility that small APP peptides or non-peptidic compounds mimicking their activity may be used therapeutically for the improvement of memory performance.

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References

  • Araki W, Kitaguchi N, Tokushima Y, Ishii K, Aratake H, Shimohama S, Nakamura S, Kimura J (1991) Trophic effect of ²-amyloid precursor protein on cerebral cortical neurons in culture. Biochem Biophys Res Commun 181 : 265–271

    Article  PubMed  CAS  Google Scholar 

  • Bhasin R, Van Nostrand WE, Saitoh T, Donets MA, Barnes EA, Quitschke WW, Goldgaber D (1991) Expression of active secreted forms of human amyloid β-protein precursor by recombinant baculovirus-infected insect cells. Proc Natl Acad Sci USA 88 : 10307–10311

    Article  PubMed  CAS  Google Scholar 

  • Bowes MP, Saitoh T, Zivin JA, Roch J-M, Uéda K (1992) A 17-mer peptide segment of the amyloid β/A4-protein (APP) reduces neurologic damage in a rabbit spinal cord ischemia model. Soc Neurosci Abstr 18 : 1437

    Google Scholar 

  • Cai XD, Golde TE, Younkin SG (1993) Release of excess amyloid beta protein from a mutant amyloid beta protein precursor. Science 259 : 514–516

    Article  PubMed  CAS  Google Scholar 

  • Chartier-Harlin M-C, Crawford F, Houlden H, Warren A, Hughes D, Fidani L, Goate A, Rossor M, Roques P, Hardy J, Mullan M (1991) Early-onset Alzheimer’s disease caused by mutations at codon 717 of the ²-amyloid precursor protein. Nature 353 : 844–846

    Article  PubMed  CAS  Google Scholar 

  • Citron M, Oltersdorf T, Haass C, McConlogue L, Hung AY, Seubert P, Vigo-Pelfrey C, Lieberburg I, Selkoe DJ (1992) Mutation of the beta-amyloid precursor protein in familial Alzheimer’s disease increases beta-protein production. Nature 360 : 672–674

    Article  PubMed  CAS  Google Scholar 

  • Cole GM, Galasko D, Shapiro IP, Saitoh T (1990) Stimulated platelets release amyloid β-protein precursor. Biochem Biophys Res Commun 170 : 288–295

    Article  PubMed  CAS  Google Scholar 

  • Cole GM, Masliah E, Shelton ER, Chan HW, Terry RD, Saitoh T (1991) Accumulation of amyloid precursor fragment of Alzheimer plaques. Neurobiol. Aging 12 : 85–91

    Article  PubMed  CAS  Google Scholar 

  • Crawford F, Hardy J, Mullan M, Goate A, Hughes D, Fidani L, Roques P, Rossor M, Chartierharlin MC (1991) Sequencing of exons 16 and 17 of the beta-amyloid precursor protein gene in 14 families with early onset of Alzheimer’s disease fails to reveal mutations in the beta-amyloid sequence. Neurosci Lett 133 : 1–2

    Article  PubMed  CAS  Google Scholar 

  • Cunningham DD, Van Nostrand WE (1991) Protease nexin-2/amyloid ²-protein precursor may function in wound repair. In: Regulation and genetic control of brain amyloid.

    Google Scholar 

  • Cunningham DD, Van Nostrand WE (1991) Protease nexin-2/amyloid ²-protein precursor may function in wound repair. Brain Res Rev 16: 95–96

    Google Scholar 

  • De Sauvage F, Octave JN (1989) A novel mRNA of the A4 amyloid precursor gene coding for a possibly secreted protein. Science 245 : 651–653

    Article  PubMed  Google Scholar 

  • Glenner GG, Wong CW (1984) Alzheimer’s disease and Down’s syndrome: sharing a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 122:1131–1135

    Article  PubMed  CAS  Google Scholar 

  • Goate A, Chartier-Harlin M-C, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, Mant R, Newton P, Rooke K, Roques P, Talbot C, Pericak-Vance M, Roses A, Williamson R, Rossor M, Owen M, Hardy J (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349 : 704–706

    Article  PubMed  CAS  Google Scholar 

  • Golde TE, Estus S, Usiak M, Younkin LH, Younkin SG (1990) Expression of β amyloid protein precursor mRNAs: recognition of a novel alternatively spliced form and quantitation in Alzheimer’s disease using PCR. Neuron 4 : 253–267

    Article  PubMed  CAS  Google Scholar 

  • Goldgaber D, Lerman MI, McBride OW, Saffiotti U, Gajdusek DC (1987) Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer’s disease. Science 235 : 877–880

    Article  PubMed  CAS  Google Scholar 

  • Goldgaber D, Schwarzman AI, Bhasin R, Gregori L, Schmechel D, Saunders AM, Roses AD, Strittmatter WJ (1993) Sequestration of amyloid β peptide. Ann NY Acad Sci 695 : 139–143

    Article  PubMed  CAS  Google Scholar 

  • Hardy JA, Higgins GA (1992) Alzheimer’s disease: The amyloid cascade hypothesis. Science 256:184–185

    Article  PubMed  CAS  Google Scholar 

  • Hendriks L, van Duijn CM, Cras P, Cruts M, Hul VW, van Harskamp F, Warren A, Mclnnis MG, Antonarakis SE, Martin J-J, Hofman A, Van Broeckhoven C (1992) Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β-amyloid precursor protein gene. Nature Genet 1: 218–221

    Article  PubMed  CAS  Google Scholar 

  • Higgins GA, Oyler GA, Neve RL, Chen KS, Gage FH (1990) Altered levels of amyloid protein precursor transcripts in the basal forebrain of behaviorally impaired aged rats. Proc Natl Acad Sci USA 87 : 3032–3036

    Article  PubMed  CAS  Google Scholar 

  • Jin L-W, Masliah E, Ninomiya H, Roch J-M, Otero DAC, Schubert D, Saitoh T (1992) Biological activity of the amyloid β/A4-protein precursor II: Neurotrophic effect of an APP peptide on a rat brain neuroblastoma cell line. Soc Neurosci Abstr 18 : 1466

    Google Scholar 

  • Joachim CL, Selkoe DJ (1992) The seminal role of beta-amyloid in the pathogenesis of Alzheimer disease. Alzheimer’s Disease Assoc Disorders. 6: 7–34

    Article  CAS  Google Scholar 

  • Joachim CL, Games D, Morris J, Ward P, Frenkel D, Selkoe D (1991) Antibodies to non-beta regions of the beta-amyloid precursor protein detect a subset of senile plaques. Am J Pathol 138 : 373–384

    PubMed  CAS  Google Scholar 

  • Johnson SA, McNeill T, Cordell B, Finch CE (1990) Relation of neuronal APP-751/APP-695 mRNA ratio and neuritic plaque density in Alzheimer’s disease. Science 248 : 854–857

    Article  PubMed  CAS  Google Scholar 

  • Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Müller-Hill B (1987) The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325 : 733–736

    Article  PubMed  CAS  Google Scholar 

  • Kitaguchi N, Takahashi Y, Tokushima Y, Shiojiri S, Ito H (1988) Novel precursor of Alzheimer’s disease amyloid protein shows protease inhibitory activity. Nature 331: 530–532

    Article  PubMed  CAS  Google Scholar 

  • Kitaguchi N, Tokushima Y, Oishi K, Takahashi Y, Shiojiri S, Nakamura S, Tanaka S, Kodaira R, Ito H (1990) Determination of amyloid β protein precursors harboring active form of proteinase inhibitors in cerebrospinal fluid of Alzheimer’s disease patients by trypsin-antibody sandwich ELISA. Biochem Biophys Res Commun 166 : 1453–1459

    Article  PubMed  CAS  Google Scholar 

  • König G, Salbaum JM, Wiestler O, Lang W, Schmitt HP, Masters CL, Beyreuther K (1991) Alternative splicing of the βA4 amyloid gene of Alzheimer’s disease in cortex of control and Alzheimer’s disease patients. Mol Brain Res 9 : 259–262

    Article  PubMed  Google Scholar 

  • Koo EH, Sisodia SS, Archer DR, Martin LJ, Weidemann A, Beyreuther K, Fischer P, Masters CL, Price DL (1989) Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proc Natl Acad Sci USA 87 : 1561–1565

    Article  Google Scholar 

  • Kosik KS (1992) Alzheimer’s disease: a cell biological perspective. Science 256 : 780–783

    Article  PubMed  CAS  Google Scholar 

  • Masliah E, Mallory M, Hansen L, Alford M, DeTeresa R, Terry R, Baudier J, Saitoh T (1992a) Localization of amyloid precursor protein in GAP43-immunoreactive aberrant sprouting neurites in Alzheimer’s disease. Brain Res 574 : 312–316

    Article  PubMed  CAS  Google Scholar 

  • Masliah E, Mallory M, Ge N, Saitoh T (1992b) Amyloid precursor protein is localized in growing neurites of neonatal rat brain. Brain Res 593 : 323–328

    Article  PubMed  CAS  Google Scholar 

  • Masliah E, Abraham C, Johnson W, Forss-Petter S, Mallory M, Terry R, Mucke L (1993) Synaptic alterations in the cortex of APP transgenic mice. J Neuropathol Exp Neurol 52 : 178

    Google Scholar 

  • Masters CL, Multhaup G, Simms G, Pottgiesser J, Martins RN, Beyreuther K (1985) Neuronal origin of a cerebral amyloid: Neurofibrillary tangles of Alzheimer’s disease contain the same protein as the amyloid plaque cores and blood vessels. EMBO J 4: 2757–2763

    PubMed  CAS  Google Scholar 

  • Mattson MP, Cheng B, Davis D, Bryant K, Lieberburg I, Rydel RE (1992) 2-amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J Neurosci 12 : 376–389

    PubMed  CAS  Google Scholar 

  • Mattson MP, Cheng B, Culwell AR, Esch FS, Lieberburg I, Rydel RE (1993) Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the betaamyloid precursor protein. Neuron 10 : 243–254

    Article  PubMed  CAS  Google Scholar 

  • Milward EA, Papadopoulos R, Fuller SJ, Moir RD, Small D, Beyreuther K, Masters CL (1992) The amyloid protein precursor of Alzheimer’s disease is a mediator of the effects of nerve growth factor on neurite outgrowth. Neuron 9 : 129–137

    Article  PubMed  CAS  Google Scholar 

  • Mullan M, Crawford F, Axelman K, Houlden H, Lilius L, Winblad, Lannfelt L (1992) A pathogenic mutation for probable Alzheimer’s disease in the APP gene at the N-terminus of ²-amyloid. Nature Genet 1: 345–347

    Article  PubMed  CAS  Google Scholar 

  • Murrell J, Farlow M, Ghetti B, Benson MD (1991) A mutation in the amyloid precursor protein associated with hereditary Alzheimer’s disease. Science 14 : 26–28

    Google Scholar 

  • Naruse S, Igarashi S, Kobayashi H, Aoki K, Inuzuka T, Kaneko K, Shimizu T, Lihara K, Kojima T, Miyatake T, Tsuki S (1991) Mis-sense mutation Val-11e in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer’s disease. Lancet 337 : 978–979

    Article  PubMed  CAS  Google Scholar 

  • Neve RL, Finch EA, Dawes LR (1988) Expression of the Alzheimer amyloid precursor gene transcripts in the human brain. Neuron 1 : 669–677

    Article  PubMed  CAS  Google Scholar 

  • Neve RL, Rogers J, Higgins GA (1990) The Alzheimer amyloid precursor related transcript lacking the β/A4 sequence is specifically increased in Alzheimer’s disease brain. Neuron 5 : 329–338

    Article  PubMed  CAS  Google Scholar 

  • Ninomiya H, Roch J-M, Sundsmo MP, Otero DAC, Saitoh T (1993) Amino acid sequence RERMS represents the active domain of amyloid β/A4 protein precursor that promotes growth. J Cell Biol 121: 879–886

    Article  PubMed  CAS  Google Scholar 

  • Oltersdorf T, Fritz LC, Schenk DB, Lieberburg I, Johson-Wood KL, Beattie EC, Ward PJ, Blacher RW, Dovey HF, Sinha S (1989) The secreted form of Alzheimer’s amyloid precursor protein with the Kunitz domain is protease nexin-II. Nature 341 : 144–147

    Article  PubMed  CAS  Google Scholar 

  • Palmert MR, Podlisny MB, Witker DS, Oltersdorf T, Younkin LH, Selkoe DJ, Younkin SG (1989) The ²-amyloid protein precursor of Alzheimer’s disease has soluble derivatives found in human brain and cerebrospinal fluid. Proc Natl Acad Sci USA 86 : 63338–6342

    Article  Google Scholar 

  • Pike CJ, Burdick D, Walencewicz AJ, Glabe CG, Cotman CW (1993) Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state. J Neurosci 13 : 1676–1687

    PubMed  CAS  Google Scholar 

  • Ponte P, Gonzalez-DeWhitt P, Shilling J, Miller J, Hsu D, Greenberg B, Davis K, Wallace W, Lieberburg I, Fuller F (1988) A new A4 amyloid mRNA contains a domain homologous to serine protease inhibitors. Nature 331 : 525–527

    Article  PubMed  CAS  Google Scholar 

  • Robakis NK, Ramakrishna N, Wolfe G, Wisniewski HM (1987) Molecular cloning and characterization of a cDNA encoding cerebrovascular and the neuritic plaque amyloid peptides. Proc Natl Acad Sci USA 84:4190–4193

    Article  PubMed  CAS  Google Scholar 

  • Robakis NK, Altstiel LD, Refolo LM, Anderson JP (1990) Function and metabolism of the protease inhibitor-containing Alzheimer amyloid precursors. In: Miyatake T, Selkoe DJ, Ihara Y (eds) Molecular biology of Alzheimer’s disease. Elsevier Science Publishers BV, Amsterdam, pp 179–188

    Google Scholar 

  • Roch J-M, Shapiro IP, Sundsmo MP, Otero DAC, Refolo LM, Robakis NK, Saitoh T (1992) Bacterial expression, purification, and functional mapping of the amyloid β/A4 protein precursor. J Biol Chem 267 : 2214–2221

    PubMed  CAS  Google Scholar 

  • Roch J-M, Masliah E, Roch-Levecq A-C, Otero DAC, Sundsmo MP, Veinbergs I, Saitoh T (1993) Increased synaptic density and memory retention by a biologically active amyloid β/A4 protein precursor peptide. Soc Neurosci Abstr 19 : 221

    Google Scholar 

  • Saitoh T, Sundsmo MP, Roch J-M, Kimura N, Cole GM, Schubert D, Oltersdorf T, Schenk DB (1989) Secreted form of amyloid ²-protein precursor is involved in the growth regulation of fibroblasts. Cell 58 : 615–622

    Article  PubMed  CAS  Google Scholar 

  • Schellenberg GD, Anderson L, O’dahl S, Wisjman EM, Sadovnick AD, Ball MJ, Larson EB, Kuku WA, Martin GM, Roses AD (1991) APP717, APP693, and PRIP gene mutations are rare in Alzheimer disease. Am J Human Genet 49 : 511–517

    CAS  Google Scholar 

  • Schubert D, Jin L-W, Saitoh T, Cole GM (1989) The regulation of amyloid ² protein precursor secretion and its modulatory role in cell adhesion. Neuron 3 : 689–694

    Article  PubMed  CAS  Google Scholar 

  • Selkoe DJ, Abraham CR, Podlisny MB, Duffy LK (1986) Isolation of low molecular weight proteins from amyloid plaques in Alzheimer’s disease. J Neurochem 146 : 1820–1834

    Google Scholar 

  • Smith RP, Higuchi DA, Broze GJ, Jr (1990) Platelet coagulation factor Xla-inhibitor, a form of Alzheimer amyloid precursor protein. Science 248 : 1126–1128

    Article  PubMed  CAS  Google Scholar 

  • Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD (1993) Apolipoprotein-E-high-avidity binding to ²-amyloid and increased frequency of type-4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 90:1977–1981

    Article  PubMed  CAS  Google Scholar 

  • Tanaka S, Nakamura S, Uéda K, Kameyama M, Shiojiri S, Takahashi Y, Kitaguchi N, Ito H (1988) Three types of amyloid precursor mRNA in human brain: their differential expression in Alzheimer’s disease. Biochem Biophys Res Commun 157 : 472–479

    Article  PubMed  CAS  Google Scholar 

  • Tanzi RE, Gusella JF, Watkins PC, Bruns GAP, St. George-Hyslop P, Van Keuren ML, Patterson D, Pagan S, Kurnit DM, Neve RL (1987) Amyloid ²-protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science 235 : 880–884

    Article  PubMed  CAS  Google Scholar 

  • Tanzi RE, MacClatchey AI, Lamperti ED, Villa-Komaroff LV, Gusella JF, Neve RL (1988) Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer’s disease. Nature 331 : 528–530

    Article  PubMed  CAS  Google Scholar 

  • Tanzi RE, Vaula G, Romano DM, Mortilla M, Huang TL, Tupler RG, Wasco W, Hyman BT, Haines JL, Jenkins BJ (1992) Assessment of amyloid beta-protein precursor gene mutations in a large set of familial and sporadic Alzheimer disease cases. Am J Human Genet 51 : 273–282

    CAS  Google Scholar 

  • Uéda K, Cole G, Sundsmo M, Katzman R, Saitoh T (1989) Decreased adhesiveness of Alzheimer’s disease fibroblasts: Is amyloid ²-protein precursor involved? Ann Neurol 25 : 246–251

    Article  PubMed  Google Scholar 

  • Van Nostrand WE, Wagner SL, Suzuki M, Choi BH, Farrow JS, Geddes JW, Cotman CW, Cunningham DD (1989) Protease nexin-II, a potent antichymotrypsin, shows identity to amyloid ²-protein precursor. Nature 341 : 546–548

    Article  PubMed  Google Scholar 

  • Van Nostrand WE, Schmaier AH, Farrow JS, Cunningham DD (1990) Protease nexin-II (amyloid β-protein precursor): a platelet granule protein. Science 248 : 745–748

    Article  PubMed  Google Scholar 

  • Weidemann A, König G, Bunke D, Fischer P, Salbaum JM, Masters CL, Beyreuther K (1989) Identification, biogenesis, and localization of precursors of Alzheimer’s disease A4 amyloid protein. Cell 57 : 115–126

    Article  PubMed  CAS  Google Scholar 

  • Yankner BA, Dawes LR, Fisher S, Villa-Komaroff L, Oster-Granite ML, Neve RL (1989) Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer’s disease. Science 245 : 417–420

    Article  PubMed  CAS  Google Scholar 

  • Yankner BA, Duffy LK, Kirschner DA (1990a) Neurotrophic and neurotoxic effects of amyloid ²-protein: reversal by tachykinin neuropeptides. Science 250 : 279–282

    Article  PubMed  CAS  Google Scholar 

  • Yankner BA, Caceres A, Duffy LK (1990b) Nerve growth factor potentiates the neurotoxicity of beta amyloid. Proc Natl Acad Sci USA 87 : 9020–9030

    Article  PubMed  CAS  Google Scholar 

  • Yoshioka K, Miki T, Katsuya T, Ogihara T, Sakaki Y (1991) The 717Val-lle substitution in amyloid precursor protein is associated with familial Alzheimer’s disease regardless of ethnic groups. Biochem Biophys Res Comm 178 : 1141–1146

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosciences, 0624, School of Medicine and Center for Molecular Genetics, University of California, 92093, San Diego, La Jolla, CA, USA

    T. Saitoh

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  1. T. Saitoh
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  2. J.-M. Roch
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  3. L.-W. Jin
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  4. H. Ninomiya
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  5. D. A. C. Otero
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  6. K. Yamamoto
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  7. E. Masliah
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Editor information

Editors and Affiliations

  1. Department of Pathology, The University of Melbourne and The Mental Health Research Institute of Victoria, Parkville, Victoria, 3025, Australia

    C. L. Masters M.D.

  2. Center for Molecular Biology, University of Heidelberg, Im Neuenheimer Feld 282, 69120, Heidelberg, Germany

    K. Beyreuther Ph.D.

  3. Hôpital Neurologique, 59, Bld Pinel, 69003, Lyon, France

    M. Trillet Prof.

  4. Fondation IPSEN, 24, rue Erlanger, 75781, Paris, France

    Y. Christen Ph.D.

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© 1994 Springer-Verlag Berlin Heidelberg

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Saitoh, T. et al. (1994). The Biological Function of Amyloid β/A4 Protein Precursor. In: Masters, C.L., Beyreuther, K., Trillet, M., Christen, Y. (eds) Amyloid Protein Precursor in Development, Aging and Alzheimer’s Disease. Research and Perspectives in Alzheimer’s Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-01135-5_9

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  • DOI: https://doi.org/10.1007/978-3-662-01135-5_9

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