Amyloid beta A4 protein

NameAmyloid beta A4 protein
Synonyms
  • A4
  • ABPP
  • AD1
  • Alzheimer disease amyloid protein
  • APP
  • APPI
  • Cerebral vascular amyloid peptide
  • CVAP
  • PN-II
  • PreA4
  • Protease nexin-II
Gene NameAPP
OrganismHuman
Amino acid sequence
>lcl|BSEQ0006619|Amyloid beta A4 protein
MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTK
TCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVG
EFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFR
GVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEE
EADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPC
RAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARD
PVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQA
KNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITAL
QAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYER
MNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTET
KTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTN
IKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITL
VMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
Number of residues770
Molecular Weight86942.715
Theoretical pI4.45
GO Classification
Functions
  • transition metal ion binding
  • peptidase activator activity
  • acetylcholine receptor binding
  • DNA binding
  • identical protein binding
  • receptor binding
  • PTB domain binding
  • serine-type endopeptidase inhibitor activity
  • heparin binding
  • enzyme binding
Processes
  • locomotory behavior
  • endocytosis
  • mRNA polyadenylation
  • adult locomotory behavior
  • cell adhesion
  • axonogenesis
  • response to yeast
  • blood coagulation
  • regulation of multicellular organism growth
  • post-Golgi vesicle-mediated transport
  • ionotropic glutamate receptor signaling pathway
  • neuron remodeling
  • innate immune response
  • mating behavior
  • neuron projection development
  • dendrite development
  • regulation of translation
  • neuron apoptotic process
  • extracellular matrix organization
  • negative regulation of endopeptidase activity
  • axon midline choice point recognition
  • cellular protein metabolic process
  • antibacterial humoral response
  • positive regulation of mitotic cell cycle
  • collateral sprouting in absence of injury
  • defense response to Gram-positive bacterium
  • defense response to Gram-negative bacterium
  • regulation of epidermal growth factor-activated receptor activity
  • protein phosphorylation
  • Notch signaling pathway
  • regulation of synapse structure or activity
  • antifungal humoral response
  • membrane organization
  • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
  • platelet degranulation
  • platelet activation
  • axon cargo transport
  • cellular copper ion homeostasis
  • visual learning
Components
  • integral component of membrane
  • axon
  • cytoplasm
  • endosome
  • cytosol
  • extracellular exosome
  • perinuclear region of cytoplasm
  • extracellular region
  • nuclear envelope lumen
  • integral component of plasma membrane
  • plasma membrane
  • intracellular membrane-bounded organelle
  • receptor complex
  • dendritic shaft
  • extracellular space
  • platelet alpha granule lumen
  • cell surface
  • coated pit
  • endosome lumen
  • trans-Golgi network membrane
  • dendritic spine
  • synapse
  • terminal bouton
  • membrane raft
  • Golgi apparatus
General FunctionTransition metal ion binding
Specific FunctionFunctions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).
Pfam Domain Function
Transmembrane Regions700-723
GenBank Protein IDNot Available
UniProtKB IDP05067
UniProtKB Entry NameA4_HUMAN
Cellular LocationMembrane
Gene sequence
>lcl|BSEQ0019416|Amyloid beta A4 protein (APP)
ATGCTGCCCGGTTTGGCACTGCTCCTGCTGGCCGCCTGGACGGCTCGGGCGCTGGAGGTA
CCCACTGATGGTAATGCTGGCCTGCTGGCTGAACCCCAGATTGCCATGTTCTGTGGCAGA
CTGAACATGCACATGAATGTCCAGAATGGGAAGTGGGATTCAGATCCATCAGGGACCAAA
ACCTGCATTGATACCAAGGAAGGCATCCTGCAGTATTGCCAAGAAGTCTACCCTGAACTG
CAGATCACCAATGTGGTAGAAGCCAACCAACCAGTGACCATCCAGAACTGGTGCAAGCGG
GGCCGCAAGCAGTGCAAGACCCATCCCCACTTTGTGATTCCCTACCGCTGCTTAGTTGGT
GAGTTTGTAAGTGATGCCCTTCTCGTTCCTGACAAGTGCAAATTCTTACACCAGGAGAGG
ATGGATGTTTGCGAAACTCATCTTCACTGGCACACCGTCGCCAAAGAGACATGCAGTGAG
AAGAGTACCAACTTGCATGACTACGGCATGTTGCTGCCCTGCGGAATTGACAAGTTCCGA
GGGGTAGAGTTTGTGTGTTGCCCACTGGCTGAAGAAAGTGACAATGTGGATTCTGCTGAT
GCGGAGGAGGATGACTCGGATGTCTGGTGGGGCGGAGCAGACACAGACTATGCAGATGGG
AGTGAAGACAAAGTAGTAGAAGTAGCAGAGGAGGAAGAAGTGGCTGAGGTGGAAGAAGAA
GAAGCCGATGATGACGAGGACGATGAGGATGGTGATGAGGTAGAGGAAGAGGCTGAGGAA
CCCTACGAAGAAGCCACAGAGAGAACCACCAGCATTGCCACCACCACCACCACCACCACA
GAGTCTGTGGAAGAGGTGGTTCGAGAGGTGTGCTCTGAACAAGCCGAGACGGGGCCGTGC
CGAGCAATGATCTCCCGCTGGTACTTTGATGTGACTGAAGGGAAGTGTGCCCCATTCTTT
TACGGCGGATGTGGCGGCAACCGGAACAACTTTGACACAGAAGAGTACTGCATGGCCGTG
TGTGGCAGCGCCATGTCCCAAAGTTTACTCAAGACTACCCAGGAACCTCTTGCCCGAGAT
CCTGTTAAACTTCCTACAACAGCAGCCAGTACCCCTGATGCCGTTGACAAGTATCTCGAG
ACACCTGGGGATGAGAATGAACATGCCCATTTCCAGAAAGCCAAAGAGAGGCTTGAGGCC
AAGCACCGAGAGAGAATGTCCCAGGTCATGAGAGAATGGGAAGAGGCAGAACGTCAAGCA
AAGAACTTGCCTAAAGCTGATAAGAAGGCAGTTATCCAGCATTTCCAGGAGAAAGTGGAA
TCTTTGGAACAGGAAGCAGCCAACGAGAGACAGCAGCTGGTGGAGACACACATGGCCAGA
GTGGAAGCCATGCTCAATGACCGCCGCCGCCTGGCCCTGGAGAACTACATCACCGCTCTG
CAGGCTGTTCCTCCTCGGCCTCGTCACGTGTTCAATATGCTAAAGAAGTATGTCCGCGCA
GAACAGAAGGACAGACAGCACACCCTAAAGCATTTCGAGCATGTGCGCATGGTGGATCCC
AAGAAAGCCGCTCAGATCCGGTCCCAGGTTATGACACACCTCCGTGTGATTTATGAGCGC
ATGAATCAGTCTCTCTCCCTGCTCTACAACGTGCCTGCAGTGGCCGAGGAGATTCAGGAT
GAAGTTGATGAGCTGCTTCAGAAAGAGCAAAACTATTCAGATGACGTCTTGGCCAACATG
ATTAGTGAACCAAGGATCAGTTACGGAAACGATGCTCTCATGCCATCTTTGACCGAAACG
AAAACCACCGTGGAGCTCCTTCCCGTGAATGGAGAGTTCAGCCTGGACGATCTCCAGCCG
TGGCATTCTTTTGGGGCTGACTCTGTGCCAGCCAACACAGAAAACGAAGTTGAGCCTGTT
GATGCCCGCCCTGCTGCCGACCGAGGACTGACCACTCGACCAGGTTCTGGGTTGACAAAT
ATCAAGACGGAGGAGATCTCTGAAGTGAAGATGGATGCAGAATTCCGACATGACTCAGGA
TATGAAGTTCATCATCAAAAATTGGTGTTCTTTGCAGAAGATGTGGGTTCAAACAAAGGT
GCAATCATTGGACTCATGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACCTTG
GTGATGCTGAAGAAGAAACAGTACACATCCATTCATCATGGTGTGGTGGAGGTTGACGCC
GCTGTCACCCCAGAGGAGCGCCACCTGTCCAAGATGCAGCAGAACGGCTACGAAAATCCA
ACCTACAAGTTCTTTGAGCAGATGCAGAACTAG
GenBank Gene IDX06989
GeneCard IDNot Available
GenAtlas IDAPP
HGNC IDHGNC:620
Chromosome Location21
LocusNot Available
References
  1. Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Muller-Hill B: The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature. 1987 Feb 19-25;325(6106):733-6. 2881207
  2. Ponte P, Gonzalez-DeWhitt P, Schilling J, Miller J, Hsu D, Greenberg B, Davis K, Wallace W, Lieberburg I, Fuller F: A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature. 1988 Feb 11;331(6156):525-7. 2893289
  3. Lemaire HG, Salbaum JM, Multhaup G, Kang J, Bayney RM, Unterbeck A, Beyreuther K, Muller-Hill B: The PreA4(695) precursor protein of Alzheimer's disease A4 amyloid is encoded by 16 exons. Nucleic Acids Res. 1989 Jan 25;17(2):517-22. 2783775
  4. Yoshikai S, Sasaki H, Doh-ura K, Furuya H, Sakaki Y: Genomic organization of the human amyloid beta-protein precursor gene. Gene. 1990 Mar 15;87(2):257-63. 2110105
  5. Yoshikai S, Sasaki H, Doh-ura K, Furuya H, Sakaki Y: Genomic organization of the human-amyloid beta-protein precursor gene. Gene. 1991 Jun 30;102(2):291-2. 1908403
  6. Konig G, Monning U, Czech C, Prior R, Banati R, Schreiter-Gasser U, Bauer J, Masters CL, Beyreuther K: Identification and differential expression of a novel alternative splice isoform of the beta A4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglial cells. J Biol Chem. 1992 May 25;267(15):10804-9. 1587857
  7. Hattori M, Tsukahara F, Furuhata Y, Tanahashi H, Hirose M, Saito M, Tsukuni S, Sakaki Y: A novel method for making nested deletions and its application for sequencing of a 300 kb region of human APP locus. Nucleic Acids Res. 1997 May 1;25(9):1802-8. 9108164
  8. Tang K, Wang C, Shen C, Sheng S, Ravid R, Jing N: Identification of a novel alternative splicing isoform of human amyloid precursor protein gene, APP639. Eur J Neurosci. 2003 Jul;18(1):102-8. 12859342
  9. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  10. Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML: The DNA sequence of human chromosome 21. Nature. 2000 May 18;405(6784):311-9. 10830953
  11. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  12. Mita S, Sadlock J, Herbert J, Schon EA: A cDNA specifying the human amyloid beta precursor protein (ABPP) encodes a 95-kDa polypeptide. Nucleic Acids Res. 1988 Oct 11;16(19):9351. 3140222
  13. La Fauci G, Lahiri DK, Salton SR, Robakis NK: Characterization of the 5'-end region and the first two exons of the beta-protein precursor gene. Biochem Biophys Res Commun. 1989 Feb 28;159(1):297-304. 2538123
  14. Van Nostrand WE, Cunningham DD: Purification of protease nexin II from human fibroblasts. J Biol Chem. 1987 Jun 25;262(18):8508-14. 3597385
  15. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. 12665801
  16. Tanzi RE, McClatchey AI, Lamperti ED, Villa-Komaroff L, Gusella JF, Neve RL: Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature. 1988 Feb 11;331(6156):528-30. 2893290
  17. Kitaguchi N, Takahashi Y, Tokushima Y, Shiojiri S, Ito H: Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature. 1988 Feb 11;331(6156):530-2. 2893291
  18. Zain SB, Salim M, Chou WG, Sajdel-Sulkowska EM, Majocha RE, Marotta CA: Molecular cloning of amyloid cDNA derived from mRNA of the Alzheimer disease brain: coding and noncoding regions of the fetal precursor mRNA are expressed in the cortex. Proc Natl Acad Sci U S A. 1988 Feb;85(3):929-33. 2893379
  19. Beher D, Hesse L, Masters CL, Multhaup G: Regulation of amyloid protein precursor (APP) binding to collagen and mapping of the binding sites on APP and collagen type I. J Biol Chem. 1996 Jan 19;271(3):1613-20. 8576160
  20. Denman RB, Rosenzcwaig R, Miller DL: A system for studying the effect(s) of familial Alzheimer disease mutations on the processing of the beta-amyloid peptide precursor. Biochem Biophys Res Commun. 1993 Apr 15;192(1):96-103. 8476439
  21. Johnstone EM, Chaney MO, Moore RE, Ward KE, Norris FH, Little SP: Alzheimer's disease amyloid peptide is encoded by two exons and shows similarity to soybean trypsin inhibitor. Biochem Biophys Res Commun. 1989 Sep 29;163(3):1248-55. 2675837
  22. Wakutani Y, Watanabe K, Adachi Y, Wada-Isoe K, Urakami K, Ninomiya H, Saido TC, Hashimoto T, Iwatsubo T, Nakashima K: Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2004 Jul;75(7):1039-42. 15201367
  23. Roher AE, Lowenson JD, Clarke S, Woods AS, Cotter RJ, Gowing E, Ball MJ: beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10836-40. 8248178
  24. Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D, Sinha S, Schlossmacher M, Whaley J, Swindlehurst C, et al.: Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. Nature. 1992 Sep 24;359(6393):325-7. 1406936
  25. Wisniewski T, Lalowski M, Levy E, Marques MR, Frangione B: The amino acid sequence of neuritic plaque amyloid from a familial Alzheimer's disease patient. Ann Neurol. 1994 Feb;35(2):245-6. 8109908
  26. Vigo-Pelfrey C, Lee D, Keim P, Lieberburg I, Schenk DB: Characterization of beta-amyloid peptide from human cerebrospinal fluid. J Neurochem. 1993 Nov;61(5):1965-8. 8229004
  27. Pardridge WM, Vinters HV, Yang J, Eisenberg J, Choi TB, Tourtellotte WW, Huebner V, Shively JE: Amyloid angiopathy of Alzheimer's disease: amino acid composition and partial sequence of a 4,200-dalton peptide isolated from cortical microvessels. J Neurochem. 1987 Nov;49(5):1394-401. 3312495
  28. Goldgaber D, Lerman MI, McBride OW, Saffiotti U, Gajdusek DC: Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science. 1987 Feb 20;235(4791):877-80. 3810169
  29. Tanzi RE, Gusella JF, Watkins PC, Bruns GA, St George-Hyslop P, Van Keuren ML, Patterson D, Pagan S, Kurnit DM, Neve RL: Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science. 1987 Feb 20;235(4791):880-4. 2949367
  30. Brinkmalm G, Portelius E, Ohrfelt A, Mattsson N, Persson R, Gustavsson MK, Vite CH, Gobom J, Mansson JE, Nilsson J, Halim A, Larson G, Ruetschi U, Zetterberg H, Blennow K, Brinkmalm A: An online nano-LC-ESI-FTICR-MS method for comprehensive characterization of endogenous fragments from amyloid beta and amyloid precursor protein in human and cat cerebrospinal fluid. J Mass Spectrom. 2012 May;47(5):591-603. doi: 10.1002/jms.2987. 22576872
  31. Sun X, He G, Song W: BACE2, as a novel APP theta-secretase, is not responsible for the pathogenesis of Alzheimer's disease in Down syndrome. FASEB J. 2006 Jul;20(9):1369-76. 16816112
  32. de Sauvage F, Octave JN: A novel mRNA of the A4 amyloid precursor gene coding for a possibly secreted protein. Science. 1989 Aug 11;245(4918):651-3. 2569763
  33. Robakis NK, Ramakrishna N, Wolfe G, Wisniewski HM: Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4190-4. 3035574
  34. Pangalos MN, Efthimiopoulos S, Shioi J, Robakis NK: The chondroitin sulfate attachment site of appican is formed by splicing out exon 15 of the amyloid precursor gene. J Biol Chem. 1995 May 5;270(18):10388-91. 7737970
  35. Walter MF, Mason PE, Mason RP: Alzheimer's disease amyloid beta peptide 25-35 inhibits lipid peroxidation as a result of its membrane interactions. Biochem Biophys Res Commun. 1997 Apr 28;233(3):760-4. 9168929
  36. Kontush A: Alzheimer's amyloid-beta as a preventive antioxidant for brain lipoproteins. Cell Mol Neurobiol. 2001 Aug;21(4):299-315. 11775062
  37. Oltersdorf T, Fritz LC, Schenk DB, Lieberburg I, Johnson-Wood KL, Beattie EC, Ward PJ, Blacher RW, Dovey HF, Sinha S: The secreted form of the Alzheimer's amyloid precursor protein with the Kunitz domain is protease nexin-II. Nature. 1989 Sep 14;341(6238):144-7. 2506449
  38. Kido H, Fukutomi A, Schilling J, Wang Y, Cordell B, Katunuma N: Protease-specificity of Kunitz inhibitor domain of Alzheimer's disease amyloid protein precursor. Biochem Biophys Res Commun. 1990 Mar 16;167(2):716-21. 1969731
  39. Bush AI, Multhaup G, Moir RD, Williamson TG, Small DH, Rumble B, Pollwein P, Beyreuther K, Masters CL: A novel zinc(II) binding site modulates the function of the beta A4 amyloid protein precursor of Alzheimer's disease. J Biol Chem. 1993 Aug 5;268(22):16109-12. 8344894
  40. Nishimoto I, Okamoto T, Matsuura Y, Takahashi S, Okamoto T, Murayama Y, Ogata E: Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G(o) Nature. 1993 Mar 4;362(6415):75-9. 8446172
  41. Hesse L, Beher D, Masters CL, Multhaup G: The beta A4 amyloid precursor protein binding to copper. FEBS Lett. 1994 Jul 25;349(1):109-16. 7913895
  42. Small DH, Nurcombe V, Reed G, Clarris H, Moir R, Beyreuther K, Masters CL: A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth. J Neurosci. 1994 Apr;14(4):2117-27. 8158260
  43. Maruyama K, Tomita T, Shinozaki K, Kume H, Asada H, Saido TC, Ishiura S, Iwatsubo T, Obata K: Familial Alzheimer's disease-linked mutations at Val717 of amyloid precursor protein are specific for the increased secretion of A beta 42(43). Biochem Biophys Res Commun. 1996 Oct 23;227(3):730-5. 8886002
  44. Chow N, Korenberg JR, Chen XN, Neve RL: APP-BP1, a novel protein that binds to the carboxyl-terminal region of the amyloid precursor protein. J Biol Chem. 1996 May 10;271(19):11339-46. 8626687
  45. Borg JP, Ooi J, Levy E, Margolis B: The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein. Mol Cell Biol. 1996 Nov;16(11):6229-41. 8887653
  46. Guenette SY, Chen J, Jondro PD, Tanzi RE: Association of a novel human FE65-like protein with the cytoplasmic domain of the beta-amyloid precursor protein. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10832-7. 8855266
  47. Mok SS, Sberna G, Heffernan D, Cappai R, Galatis D, Clarris HJ, Sawyer WH, Beyreuther K, Masters CL, Small DH: Expression and analysis of heparin-binding regions of the amyloid precursor protein of Alzheimer's disease. FEBS Lett. 1997 Oct 6;415(3):303-7. 9357988
  48. Yan SD, Fu J, Soto C, Chen X, Zhu H, Al-Mohanna F, Collison K, Zhu A, Stern E, Saido T, Tohyama M, Ogawa S, Roher A, Stern D: An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease. Nature. 1997 Oct 16;389(6652):689-95. 9338779
  49. Zheng P, Eastman J, Vande Pol S, Pimplikar SW: PAT1, a microtubule-interacting protein, recognizes the basolateral sorting signal of amyloid precursor protein. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14745-50. 9843960
  50. Liu ST, Howlett G, Barrow CJ: Histidine-13 is a crucial residue in the zinc ion-induced aggregation of the A beta peptide of Alzheimer's disease. Biochemistry. 1999 Jul 20;38(29):9373-8. 10413512
  51. Varadarajan S, Yatin S, Kanski J, Jahanshahi F, Butterfield DA: Methionine residue 35 is important in amyloid beta-peptide-associated free radical oxidative stress. Brain Res Bull. 1999 Sep 15;50(2):133-41. 10535332
  52. Tomita S, Ozaki T, Taru H, Oguchi S, Takeda S, Yagi Y, Sakiyama S, Kirino Y, Suzuki T: Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein. J Biol Chem. 1999 Jan 22;274(4):2243-54. 9890987
  53. Perez RG, Soriano S, Hayes JD, Ostaszewski B, Xia W, Selkoe DJ, Chen X, Stokin GB, Koo EH: Mutagenesis identifies new signals for beta-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Abeta42. J Biol Chem. 1999 Jul 2;274(27):18851-6. 10383380
  54. Ruiz FH, Gonzalez M, Bodini M, Opazo C, Inestrosa NC: Cysteine 144 is a key residue in the copper reduction by the beta-amyloid precursor protein. J Neurochem. 1999 Sep;73(3):1288-92. 10461923
  55. Tokuda T, Calero M, Matsubara E, Vidal R, Kumar A, Permanne B, Zlokovic B, Smith JD, Ladu MJ, Rostagno A, Frangione B, Ghiso J: Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer's amyloid beta peptides. Biochem J. 2000 Jun 1;348 Pt 2:359-65. 10816430
  56. Wang HY, Lee DH, D'Andrea MR, Peterson PA, Shank RP, Reitz AB: beta-Amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology. J Biol Chem. 2000 Feb 25;275(8):5626-32. 10681545
  57. Passer B, Pellegrini L, Russo C, Siegel RM, Lenardo MJ, Schettini G, Bachmann M, Tabaton M, D'Adamio L: Generation of an apoptotic intracellular peptide by gamma-secretase cleavage of Alzheimer's amyloid beta protein precursor. J Alzheimers Dis. 2000 Nov;2(3-4):289-301. 12214090
  58. Yazawa H, Yu ZX, Takeda, Le Y, Gong W, Ferrans VJ, Oppenheim JJ, Li CC, Wang JM: Beta amyloid peptide (Abeta42) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages. FASEB J. 2001 Nov;15(13):2454-62. 11689470
  59. Kajkowski EM, Lo CF, Ning X, Walker S, Sofia HJ, Wang W, Edris W, Chanda P, Wagner E, Vile S, Ryan K, McHendry-Rinde B, Smith SC, Wood A, Rhodes KJ, Kennedy JD, Bard J, Jacobsen JS, Ozenberger BA: beta -Amyloid peptide-induced apoptosis regulated by a novel protein containing a g protein activation module. J Biol Chem. 2001 Jun 1;276(22):18748-56. Epub 2001 Feb 20. 11278849
  60. Curtain CC, Ali F, Volitakis I, Cherny RA, Norton RS, Beyreuther K, Barrow CJ, Masters CL, Bush AI, Barnham KJ: Alzheimer's disease amyloid-beta binds copper and zinc to generate an allosterically ordered membrane-penetrating structure containing superoxide dismutase-like subunits. J Biol Chem. 2001 Jun 8;276(23):20466-73. Epub 2001 Mar 27. 11274207
  61. Scheuermann S, Hambsch B, Hesse L, Stumm J, Schmidt C, Beher D, Bayer TA, Beyreuther K, Multhaup G: Homodimerization of amyloid precursor protein and its implication in the amyloidogenic pathway of Alzheimer's disease. J Biol Chem. 2001 Sep 7;276(36):33923-9. Epub 2001 Jul 3. 11438549
  62. Kimberly WT, Zheng JB, Guenette SY, Selkoe DJ: The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner. J Biol Chem. 2001 Oct 26;276(43):40288-92. Epub 2001 Sep 5. 11544248
  63. Ohsawa I, Takamura C, Kohsaka S: Fibulin-1 binds the amino-terminal head of beta-amyloid precursor protein and modulates its physiological function. J Neurochem. 2001 Mar;76(5):1411-20. 11238726
  64. Rank KB, Pauley AM, Bhattacharya K, Wang Z, Evans DB, Fleck TJ, Johnston JA, Sharma SK: Direct interaction of soluble human recombinant tau protein with Abeta 1-42 results in tau aggregation and hyperphosphorylation by tau protein kinase II. FEBS Lett. 2002 Mar 13;514(2-3):263-8. 11943163
  65. Scheinfeld MH, Roncarati R, Vito P, Lopez PA, Abdallah M, D'Adamio L: Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) binds the cytoplasmic domain of the Alzheimer's beta-amyloid precursor protein (APP). J Biol Chem. 2002 Feb 1;277(5):3767-75. Epub 2001 Nov 27. 11724784
  66. White AR, Multhaup G, Galatis D, McKinstry WJ, Parker MW, Pipkorn R, Beyreuther K, Masters CL, Cappai R: Contrasting, species-dependent modulation of copper-mediated neurotoxicity by the Alzheimer's disease amyloid precursor protein. J Neurosci. 2002 Jan 15;22(2):365-76. 11784781
  67. Bush AI, Tanzi RE: The galvanization of beta-amyloid in Alzheimer's disease. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7317-9. 12032279
  68. Watanabe N, Araki W, Chui DH, Makifuchi T, Ihara Y, Tabira T: Glypican-1 as an Abeta binding HSPG in the human brain: its localization in DIG domains and possible roles in the pathogenesis of Alzheimer's disease. FASEB J. 2004 Jun;18(9):1013-5. Epub 2004 Apr 14. 15084524
  69. Ghersi E, Noviello C, D'Adamio L: Amyloid-beta protein precursor (AbetaPP) intracellular domain-associated protein-1 proteins bind to AbetaPP and modulate its processing in an isoform-specific manner. J Biol Chem. 2004 Nov 19;279(47):49105-12. Epub 2004 Sep 3. 15347684
  70. Suzuki T, Oishi M, Marshak DR, Czernik AJ, Nairn AC, Greengard P: Cell cycle-dependent regulation of the phosphorylation and metabolism of the Alzheimer amyloid precursor protein. EMBO J. 1994 Mar 1;13(5):1114-22. 8131745
  71. Walter J, Capell A, Hung AY, Langen H, Schnolzer M, Thinakaran G, Sisodia SS, Selkoe DJ, Haass C: Ectodomain phosphorylation of beta-amyloid precursor protein at two distinct cellular locations. J Biol Chem. 1997 Jan 17;272(3):1896-903. 8999878
  72. Multhaup G, Ruppert T, Schlicksupp A, Hesse L, Bill E, Pipkorn R, Masters CL, Beyreuther K: Copper-binding amyloid precursor protein undergoes a site-specific fragmentation in the reduction of hydrogen peroxide. Biochemistry. 1998 May 19;37(20):7224-30. 9585534
  73. Gervais FG, Xu D, Robertson GS, Vaillancourt JP, Zhu Y, Huang J, LeBlanc A, Smith D, Rigby M, Shearman MS, Clarke EE, Zheng H, Van Der Ploeg LH, Ruffolo SC, Thornberry NA, Xanthoudakis S, Zamboni RJ, Roy S, Nicholson DW: Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation. Cell. 1999 Apr 30;97(3):395-406. 10319819
  74. Ando K, Oishi M, Takeda S, Iijima K, Isohara T, Nairn AC, Kirino Y, Greengard P, Suzuki T: Role of phosphorylation of Alzheimer's amyloid precursor protein during neuronal differentiation. J Neurosci. 1999 Jun 1;19(11):4421-7. 10341243
  75. Walter J, Schindzielorz A, Hartung B, Haass C: Phosphorylation of the beta-amyloid precursor protein at the cell surface by ectocasein kinases 1 and 2. J Biol Chem. 2000 Aug 4;275(31):23523-9. 10806211
  76. Lu DC, Rabizadeh S, Chandra S, Shayya RF, Ellerby LM, Ye X, Salvesen GS, Koo EH, Bredesen DE: A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor. Nat Med. 2000 Apr;6(4):397-404. 10742146
  77. Ando K, Iijima KI, Elliott JI, Kirino Y, Suzuki T: Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of beta-amyloid. J Biol Chem. 2001 Oct 26;276(43):40353-61. Epub 2001 Aug 21. 11517218
  78. Standen CL, Brownlees J, Grierson AJ, Kesavapany S, Lau KF, McLoughlin DM, Miller CC: Phosphorylation of thr(668) in the cytoplasmic domain of the Alzheimer's disease amyloid precursor protein by stress-activated protein kinase 1b (Jun N-terminal kinase-3). J Neurochem. 2001 Jan;76(1):316-20. 11146006
  79. Weidemann A, Eggert S, Reinhard FB, Vogel M, Paliga K, Baier G, Masters CL, Beyreuther K, Evin G: A novel epsilon-cleavage within the transmembrane domain of the Alzheimer amyloid precursor protein demonstrates homology with Notch processing. Biochemistry. 2002 Feb 26;41(8):2825-35. 11851430
  80. Tarr PE, Roncarati R, Pelicci G, Pelicci PG, D'Adamio L: Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc. J Biol Chem. 2002 May 10;277(19):16798-804. Epub 2002 Mar 4. 11877420
  81. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. 16335952
  82. Dyrks T, Weidemann A, Multhaup G, Salbaum JM, Lemaire HG, Kang J, Muller-Hill B, Masters CL, Beyreuther K: Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease. EMBO J. 1988 Apr;7(4):949-57. 2900137
  83. Annaert W, De Strooper B: A cell biological perspective on Alzheimer's disease. Annu Rev Cell Dev Biol. 2002;18:25-51. Epub 2002 Apr 2. 12142279
  84. Andersen OM, Reiche J, Schmidt V, Gotthardt M, Spoelgen R, Behlke J, von Arnim CA, Breiderhoff T, Jansen P, Wu X, Bales KR, Cappai R, Masters CL, Gliemann J, Mufson EJ, Hyman BT, Paul SM, Nykjaer A, Willnow TE: Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13461-6. Epub 2005 Sep 7. 16174740
  85. Nakaya T, Kawai T, Suzuki T: Regulation of FE65 nuclear translocation and function by amyloid beta-protein precursor in osmotically stressed cells. J Biol Chem. 2008 Jul 4;283(27):19119-31. doi: 10.1074/jbc.M801827200. Epub 2008 May 9. 18468999
  86. Matsuda S, Matsuda Y, D'Adamio L: BRI3 inhibits amyloid precursor protein processing in a mechanistically distinct manner from its homologue dementia gene BRI2. J Biol Chem. 2009 Jun 5;284(23):15815-25. doi: 10.1074/jbc.M109.006403. Epub 2009 Apr 14. 19366692
  87. Nikolaev A, McLaughlin T, O'Leary DD, Tessier-Lavigne M: APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature. 2009 Feb 19;457(7232):981-9. doi: 10.1038/nature07767. 19225519
  88. Takuma K, Fang F, Zhang W, Yan S, Fukuzaki E, Du H, Sosunov A, McKhann G, Funatsu Y, Nakamichi N, Nagai T, Mizoguchi H, Ibi D, Hori O, Ogawa S, Stern DM, Yamada K, Yan SS: RAGE-mediated signaling contributes to intraneuronal transport of amyloid-beta and neuronal dysfunction. Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20021-6. doi: 10.1073/pnas.0905686106. Epub 2009 Nov 9. 19901339
  89. He G, Luo W, Li P, Remmers C, Netzer WJ, Hendrick J, Bettayeb K, Flajolet M, Gorelick F, Wennogle LP, Greengard P: Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease. Nature. 2010 Sep 2;467(7311):95-8. doi: 10.1038/nature09325. 20811458
  90. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  91. Halim A, Brinkmalm G, Ruetschi U, Westman-Brinkmalm A, Portelius E, Zetterberg H, Blennow K, Larson G, Nilsson J: Site-specific characterization of threonine, serine, and tyrosine glycosylations of amyloid precursor protein/amyloid beta-peptides in human cerebrospinal fluid. Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11848-53. doi: 10.1073/pnas.1102664108. Epub 2011 Jun 28. 21712440
  92. Zhang C, Liu Y, Gilthorpe J, van der Maarel JR: MRP14 (S100A9) protein interacts with Alzheimer beta-amyloid peptide and induces its fibrillization. PLoS One. 2012;7(3):e32953. doi: 10.1371/journal.pone.0032953. Epub 2012 Mar 22. 22457725
  93. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  94. Cruchaga C, Karch CM, Jin SC, Benitez BA, Cai Y, Guerreiro R, Harari O, Norton J, Budde J, Bertelsen S, Jeng AT, Cooper B, Skorupa T, Carrell D, Levitch D, Hsu S, Choi J, Ryten M, Hardy J, Ryten M, Trabzuni D, Weale ME, Ramasamy A, Smith C, Sassi C, Bras J, Gibbs JR, Hernandez DG, Lupton MK, Powell J, Forabosco P, Ridge PG, Corcoran CD, Tschanz JT, Norton MC, Munger RG, Schmutz C, Leary M, Demirci FY, Bamne MN, Wang X, Lopez OL, Ganguli M, Medway C, Turton J, Lord J, Braae A, Barber I, Brown K, Passmore P, Craig D, Johnston J, McGuinness B, Todd S, Heun R, Kolsch H, Kehoe PG, Hooper NM, Vardy ER, Mann DM, Pickering-Brown S, Brown K, Kalsheker N, Lowe J, Morgan K, David Smith A, Wilcock G, Warden D, Holmes C, Pastor P, Lorenzo-Betancor O, Brkanac Z, Scott E, Topol E, Morgan K, Rogaeva E, Singleton AB, Hardy J, Kamboh MI, St George-Hyslop P, Cairns N, Morris JC, Kauwe JS, Goate AM: Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease. Nature. 2014 Jan 23;505(7484):550-4. doi: 10.1038/nature12825. Epub 2013 Dec 11. 24336208
  95. Fernandez-Echevarria C, Diaz M, Ferrer I, Canerina-Amaro A, Marin R: Abeta promotes VDAC1 channel dephosphorylation in neuronal lipid rafts. Relevance to the mechanisms of neurotoxicity in Alzheimer's disease. Neuroscience. 2014 Oct 10;278:354-66. doi: 10.1016/j.neuroscience.2014.07.079. Epub 2014 Aug 26. 25168729
  96. Tagliabracci VS, Wiley SE, Guo X, Kinch LN, Durrant E, Wen J, Xiao J, Cui J, Nguyen KB, Engel JL, Coon JJ, Grishin N, Pinna LA, Pagliarini DJ, Dixon JE: A Single Kinase Generates the Majority of the Secreted Phosphoproteome. Cell. 2015 Jun 18;161(7):1619-32. doi: 10.1016/j.cell.2015.05.028. 26091039
  97. Hynes TR, Randal M, Kennedy LA, Eigenbrot C, Kossiakoff AA: X-ray crystal structure of the protease inhibitor domain of Alzheimer's amyloid beta-protein precursor. Biochemistry. 1990 Oct 30;29(43):10018-22. 2125487
  98. Heald SL, Tilton RF Jr, Hammond LJ, Lee A, Bayney RM, Kamarck ME, Ramabhadran TV, Dreyer RN, Davis G, Unterbeck A, et al.: Sequential NMR resonance assignment and structure determination of the Kunitz-type inhibitor domain of the Alzheimer's beta-amyloid precursor protein. Biochemistry. 1991 Oct 29;30(43):10467-78. 1718421
  99. Talafous J, Marcinowski KJ, Klopman G, Zagorski MG: Solution structure of residues 1-28 of the amyloid beta-peptide. Biochemistry. 1994 Jun 28;33(25):7788-96. 7516706
  100. Sticht H, Bayer P, Willbold D, Dames S, Hilbich C, Beyreuther K, Frank RW, Rosch P: Structure of amyloid A4-(1-40)-peptide of Alzheimer's disease. Eur J Biochem. 1995 Oct 1;233(1):293-8. 7588758
  101. Kohno T, Kobayashi K, Maeda T, Sato K, Takashima A: Three-dimensional structures of the amyloid beta peptide (25-35) in membrane-mimicking environment. Biochemistry. 1996 Dec 17;35(50):16094-104. 8973180
  102. Scheidig AJ, Hynes TR, Pelletier LA, Wells JA, Kossiakoff AA: Crystal structures of bovine chymotrypsin and trypsin complexed to the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) and basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with altered specificities. Protein Sci. 1997 Sep;6(9):1806-24. 9300481
  103. Coles M, Bicknell W, Watson AA, Fairlie DP, Craik DJ: Solution structure of amyloid beta-peptide(1-40) in a water-micelle environment. Is the membrane-spanning domain where we think it is? Biochemistry. 1998 Aug 4;37(31):11064-77. 9693002
  104. Rossjohn J, Cappai R, Feil SC, Henry A, McKinstry WJ, Galatis D, Hesse L, Multhaup G, Beyreuther K, Masters CL, Parker MW: Crystal structure of the N-terminal, growth factor-like domain of Alzheimer amyloid precursor protein. Nat Struct Biol. 1999 Apr;6(4):327-31. 10201399
  105. Miravalle L, Tokuda T, Chiarle R, Giaccone G, Bugiani O, Tagliavini F, Frangione B, Ghiso J: Substitutions at codon 22 of Alzheimer's abeta peptide induce diverse conformational changes and apoptotic effects in human cerebral endothelial cells. J Biol Chem. 2000 Sep 1;275(35):27110-6. 10821838
  106. Zhang S, Iwata K, Lachenmann MJ, Peng JW, Li S, Stimson ER, Lu Y, Felix AM, Maggio JE, Lee JP: The Alzheimer's peptide a beta adopts a collapsed coil structure in water. J Struct Biol. 2000 Jun;130(2-3):130-41. 10940221
  107. Poulsen SA, Watson AA, Fairlie DP, Craik DJ: Solution structures in aqueous SDS micelles of two amyloid beta peptides of A beta(1-28) mutated at the alpha-secretase cleavage site (K16E, K16F). J Struct Biol. 2000 Jun;130(2-3):142-52. 10940222
  108. Wang Y, Ha Y: The X-ray structure of an antiparallel dimer of the human amyloid precursor protein E2 domain. Mol Cell. 2004 Aug 13;15(3):343-53. 15304215
  109. Shen Y, Joachimiak A, Rosner MR, Tang WJ: Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism. Nature. 2006 Oct 19;443(7113):870-4. Epub 2006 Oct 11. 17051221
  110. Kong GK, Adams JJ, Cappai R, Parker MW: Structure of Alzheimer's disease amyloid precursor protein copper-binding domain at atomic resolution. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Oct 1;63(Pt 10):819-24. Epub 2007 Sep 19. 17909280
  111. Kong GK, Adams JJ, Harris HH, Boas JF, Curtain CC, Galatis D, Masters CL, Barnham KJ, McKinstry WJ, Cappai R, Parker MW: Structural studies of the Alzheimer's amyloid precursor protein copper-binding domain reveal how it binds copper ions. J Mol Biol. 2007 Mar 16;367(1):148-61. Epub 2006 Dec 21. 17239395
  112. Gardberg AS, Dice LT, Ou S, Rich RL, Helmbrecht E, Ko J, Wetzel R, Myszka DG, Patterson PH, Dealwis C: Molecular basis for passive immunotherapy of Alzheimer's disease. Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15659-64. Epub 2007 Sep 25. 17895381
  113. Basi GS, Feinberg H, Oshidari F, Anderson J, Barbour R, Baker J, Comery TA, Diep L, Gill D, Johnson-Wood K, Goel A, Grantcharova K, Lee M, Li J, Partridge A, Griswold-Prenner I, Piot N, Walker D, Widom A, Pangalos MN, Seubert P, Jacobsen JS, Schenk D, Weis WI: Structural correlates of antibodies associated with acute reversal of amyloid beta-related behavioral deficits in a mouse model of Alzheimer disease. J Biol Chem. 2010 Jan 29;285(5):3417-27. doi: 10.1074/jbc.M109.045187. Epub 2009 Nov 18. 19923222
  114. Dahms SO, Hoefgen S, Roeser D, Schlott B, Guhrs KH, Than ME: Structure and biochemical analysis of the heparin-induced E1 dimer of the amyloid precursor protein. Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5381-6. doi: 10.1073/pnas.0911326107. Epub 2010 Mar 8. 20212142
  115. Hardy J: Framing beta-amyloid. Nat Genet. 1992 Jul;1(4):233-4. 1363811
  116. Levy E, Carman MD, Fernandez-Madrid IJ, Power MD, Lieberburg I, van Duinen SG, Bots GT, Luyendijk W, Frangione B: Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science. 1990 Jun 1;248(4959):1124-6. 2111584
  117. Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, et al.: Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature. 1991 Feb 21;349(6311):704-6. 1671712
  118. Yoshioka K, Miki T, Katsuya T, Ogihara T, Sakaki Y: The 717Val----Ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups. Biochem Biophys Res Commun. 1991 Aug 15;178(3):1141-6. 1908231
  119. Naruse S, Igarashi S, Kobayashi H, Aoki K, Inuzuka T, Kaneko K, Shimizu T, Iihara K, Kojima T, Miyatake T, et al.: Mis-sense mutation Val----Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease. Lancet. 1991 Apr 20;337(8747):978-9. 1678058
  120. Chartier-Harlin MC, Crawford F, Houlden H, Warren A, Hughes D, Fidani L, Goate A, Rossor M, Roques P, Hardy J, et al.: Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. Nature. 1991 Oct 31;353(6347):844-6. 1944558
  121. Murrell J, Farlow M, Ghetti B, Benson MD: A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science. 1991 Oct 4;254(5028):97-9. 1925564
  122. Kamino K, Orr HT, Payami H, Wijsman EM, Alonso ME, Pulst SM, Anderson L, O'dahl S, Nemens E, White JA, et al.: Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region. Am J Hum Genet. 1992 Nov;51(5):998-1014. 1415269
  123. Hendriks L, van Duijn CM, Cras P, Cruts M, Van Hul W, van Harskamp F, Warren A, McInnis MG, Antonarakis SE, Martin JJ, et al.: Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the beta-amyloid precursor protein gene. Nat Genet. 1992 Jun;1(3):218-21. 1303239
  124. Mullan M, Crawford F, Axelman K, Houlden H, Lilius L, Winblad B, Lannfelt L: A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid. Nat Genet. 1992 Aug;1(5):345-7. 1302033
  125. Jones CT, Morris S, Yates CM, Moffoot A, Sharpe C, Brock DJ, St Clair D: Mutation in codon 713 of the beta amyloid precursor protein gene presenting with schizophrenia. Nat Genet. 1992 Jul;1(4):306-9. 1307241
  126. Carter DA, Desmarais E, Bellis M, Campion D, Clerget-Darpoux F, Brice A, Agid Y, Jaillard-Serradt A, Mallet J: More missense in amyloid gene. Nat Genet. 1992 Dec;2(4):255-6. 1303275
  127. Liepnieks JJ, Ghetti B, Farlow M, Roses AD, Benson MD: Characterization of amyloid fibril beta-peptide in familial Alzheimer's disease with APP717 mutations. Biochem Biophys Res Commun. 1993 Dec 15;197(2):386-92. 8267572
  128. Peacock ML, Murman DL, Sima AA, Warren JT Jr, Roses AD, Fink JK: Novel amyloid precursor protein gene mutation (codon 665Asp) in a patient with late-onset Alzheimer's disease. Ann Neurol. 1994 Apr;35(4):432-8. 8154870
  129. Farlow M, Murrell J, Ghetti B, Unverzagt F, Zeldenrust S, Benson M: Clinical characteristics in a kindred with early-onset Alzheimer's disease and their linkage to a G-->T change at position 2149 of the amyloid precursor protein gene. Neurology. 1994 Jan;44(1):105-11. 8290042
  130. Brooks WS, Martins RN, De Voecht J, Nicholson GA, Schofield PR, Kwok JB, Fisher C, Yeung LU, Van Broeckhoven C: A mutation in codon 717 of the amyloid precursor protein gene in an Australian family with Alzheimer's disease. Neurosci Lett. 1995 Oct 27;199(3):183-6. 8577393
  131. Eckman CB, Mehta ND, Crook R, Perez-tur J, Prihar G, Pfeiffer E, Graff-Radford N, Hinder P, Yager D, Zenk B, Refolo LM, Prada CM, Younkin SG, Hutton M, Hardy J: A new pathogenic mutation in the APP gene (I716V) increases the relative proportion of A beta 42(43). Hum Mol Genet. 1997 Nov;6(12):2087-9. 9328472
  132. Cras P, van Harskamp F, Hendriks L, Ceuterick C, van Duijn CM, Stefanko SZ, Hofman A, Kros JM, Van Broeckhoven C, Martin JJ: Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692Ala-->Gly mutation. Acta Neuropathol. 1998 Sep;96(3):253-60. 9754958
  133. Ancolio K, Dumanchin C, Barelli H, Warter JM, Brice A, Campion D, Frebourg T, Checler F: Unusual phenotypic alteration of beta amyloid precursor protein (betaAPP) maturation by a new Val-715 --> Met betaAPP-770 mutation responsible for probable early-onset Alzheimer's disease. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4119-24. 10097173
  134. Finckh U, Muller-Thomsen T, Mann U, Eggers C, Marksteiner J, Meins W, Binetti G, Alberici A, Hock C, Nitsch RM, Gal A: High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. Am J Hum Genet. 2000 Jan;66(1):110-7. 10631141
  135. Kwok JB, Li QX, Hallupp M, Whyte S, Ames D, Beyreuther K, Masters CL, Schofield PR: Novel Leu723Pro amyloid precursor protein mutation increases amyloid beta42(43) peptide levels and induces apoptosis. Ann Neurol. 2000 Feb;47(2):249-53. 10665499
  136. Murrell JR, Hake AM, Quaid KA, Farlow MR, Ghetti B: Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein gene. Arch Neurol. 2000 Jun;57(6):885-7. 10867787
  137. Kumar-Singh S, De Jonghe C, Cruts M, Kleinert R, Wang R, Mercken M, De Strooper B, Vanderstichele H, Lofgren A, Vanderhoeven I, Backhovens H, Vanmechelen E, Kroisel PM, Van Broeckhoven C: Nonfibrillar diffuse amyloid deposition due to a gamma(42)-secretase site mutation points to an essential role for N-truncated A beta(42) in Alzheimer's disease. Hum Mol Genet. 2000 Nov 1;9(18):2589-98. 11063718
  138. Grabowski TJ, Cho HS, Vonsattel JP, Rebeck GW, Greenberg SM: Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy. Ann Neurol. 2001 Jun;49(6):697-705. 11409420
  139. Walsh DM, Hartley DM, Condron MM, Selkoe DJ, Teplow DB: In vitro studies of amyloid beta-protein fibril assembly and toxicity provide clues to the aetiology of Flemish variant (Ala692-->Gly) Alzheimer's disease. Biochem J. 2001 May 1;355(Pt 3):869-77. 11311152
  140. Nilsberth C, Westlind-Danielsson A, Eckman CB, Condron MM, Axelman K, Forsell C, Stenh C, Luthman J, Teplow DB, Younkin SG, Naslund J, Lannfelt L: The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. Nat Neurosci. 2001 Sep;4(9):887-93. 11528419
  141. Pasalar P, Najmabadi H, Noorian AR, Moghimi B, Jannati A, Soltanzadeh A, Krefft T, Crook R, Hardy J: An Iranian family with Alzheimer's disease caused by a novel APP mutation (Thr714Ala). Neurology. 2002 May 28;58(10):1574-5. 12034808
  142. Greenberg SM, Shin Y, Grabowski TJ, Cooper GE, Rebeck GW, Iglesias S, Chapon F, Tournier-Lasserve E, Baron JC: Hemorrhagic stroke associated with the Iowa amyloid precursor protein mutation. Neurology. 2003 Mar 25;60(6):1020-2. 12654973
  143. Rossi G, Giaccone G, Maletta R, Morbin M, Capobianco R, Mangieri M, Giovagnoli AR, Bizzi A, Tomaino C, Perri M, Di Natale M, Tagliavini F, Bugiani O, Bruni AC: A family with Alzheimer disease and strokes associated with A713T mutation of the APP gene. Neurology. 2004 Sep 14;63(5):910-2. 15365148
  144. Obici L, Demarchi A, de Rosa G, Bellotti V, Marciano S, Donadei S, Arbustini E, Palladini G, Diegoli M, Genovese E, Ferrari G, Coverlizza S, Merlini G: A novel AbetaPP mutation exclusively associated with cerebral amyloid angiopathy. Ann Neurol. 2005 Oct;58(4):639-44. 16178030
  145. Edwards-Lee T, Ringman JM, Chung J, Werner J, Morgan A, St George Hyslop P, Thompson P, Dutton R, Mlikotic A, Rogaeva E, Hardy J: An African American family with early-onset Alzheimer disease and an APP (T714I) mutation. Neurology. 2005 Jan 25;64(2):377-9. 15668448
  146. Bugiani O, Giaccone G, Rossi G, Mangieri M, Capobianco R, Morbin M, Mazzoleni G, Cupidi C, Marcon G, Giovagnoli A, Bizzi A, Di Fede G, Puoti G, Carella F, Salmaggi A, Romorini A, Patruno GM, Magoni M, Padovani A, Tagliavini F: Hereditary cerebral hemorrhage with amyloidosis associated with the E693K mutation of APP. Arch Neurol. 2010 Aug;67(8):987-95. doi: 10.1001/archneurol.2010.178. 20697050