Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Aug 1989; 86(16): 6338–6342.
PMCID: PMC297834

The beta-amyloid protein precursor of Alzheimer disease has soluble derivatives found in human brain and cerebrospinal fluid.

Abstract

In this study, we use antisera to synthetic beta-amyloid protein precursor (beta APP) peptides to identify, in human brain and cerebrospinal fluid (CSF), soluble approximately 125- and approximately 105-kDa derivatives of the beta APP that lack the carboxyl terminus of the full-length, membrane-associated forms. We show that the soluble approximately 125-kDa beta APP derivative contains the Kunitz protease inhibitor domain, whereas the approximately 105-kDa form does not, and we confirm that these two proteins are soluble beta APP derivatives by purifying each from human CSF and directly sequencing its amino terminus.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Glenner GG, Wong CW. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984 May 16;120(3):885–890. [PubMed]
  • Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4245–4249. [PMC free article] [PubMed]
  • Selkoe DJ, Abraham CR, Podlisny MB, Duffy LK. Isolation of low-molecular-weight proteins from amyloid plaque fibers in Alzheimer's disease. J Neurochem. 1986 Jun;46(6):1820–1834. [PubMed]
  • 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):877–880. [PubMed]
  • Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Müller-Hill B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature. 1987 Feb 19;325(6106):733–736. [PubMed]
  • 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):4190–4194. [PMC free article] [PubMed]
  • 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):880–884. [PubMed]
  • 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):530–532. [PubMed]
  • 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):525–527. [PubMed]
  • 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):528–530. [PubMed]
  • Dyrks T, Weidemann A, Multhaup G, Salbaum JM, Lemaire HG, Kang J, Müller-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):949–957. [PMC free article] [PubMed]
  • Selkoe DJ, Podlisny MB, Joachim CL, Vickers EA, Lee G, Fritz LC, Oltersdorf T. Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7341–7345. [PMC free article] [PubMed]
  • Palmert MR, Podlisny MB, Witker DS, Oltersdorf T, Younkin LH, Selkoe DJ, Younkin SG. Antisera to an amino-terminal peptide detect the amyloid protein precursor of Alzheimer's disease and recognize senile plaques. Biochem Biophys Res Commun. 1988 Oct 14;156(1):432–437. [PubMed]
  • Scott J, Urdea M, Quiroga M, Sanchez-Pescador R, Fong N, Selby M, Rutter WJ, Bell GI. Structure of a mouse submaxillary messenger RNA encoding epidermal growth factor and seven related proteins. Science. 1983 Jul 15;221(4607):236–240. [PubMed]
  • Doolittle RF, Feng DF, Johnson MS. Computer-based characterization of epidermal growth factor precursor. Nature. 1984 Feb 9;307(5951):558–560. [PubMed]
  • Leung DW, Spencer SA, Cachianes G, Hammonds RG, Collins C, Henzel WJ, Barnard R, Waters MJ, Wood WI. Growth hormone receptor and serum binding protein: purification, cloning and expression. Nature. 1987 Dec 10;330(6148):537–543. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [PMC free article] [PubMed]
  • Matsudaira P. Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes. J Biol Chem. 1987 Jul 25;262(21):10035–10038. [PubMed]
  • Castaño EM, Ghiso J, Prelli F, Gorevic PD, Migheli A, Frangione B. In vitro formation of amyloid fibrils from two synthetic peptides of different lengths homologous to Alzheimer's disease beta-protein. Biochem Biophys Res Commun. 1986 Dec 15;141(2):782–789. [PubMed]
  • Kirschner DA, Inouye H, Duffy LK, Sinclair A, Lind M, Selkoe DJ. Synthetic peptide homologous to beta protein from Alzheimer disease forms amyloid-like fibrils in vitro. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6953–6957. [PMC free article] [PubMed]
  • Perry G, Lipphardt S, Mulvihill P, Kancherla M, Mijares M, Gambetti P, Sharma S, Maggiora L, Cornette J, Lobl T, et al. Amyloid precursor protein in senile plaques of Alzheimer disease. Lancet. 1988 Sep 24;2(8613):746–746. [PubMed]
  • Cohen ML, Golde TE, Usiak MF, Younkin LH, Younkin SG. In situ hybridization of nucleus basalis neurons shows increased beta-amyloid mRNA in Alzheimer disease. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1227–1231. [PMC free article] [PubMed]
  • Palmert MR, Golde TE, Cohen ML, Kovacs DM, Tanzi RE, Gusella JF, Usiak MF, Younkin LH, Younkin SG. Amyloid protein precursor messenger RNAs: differential expression in Alzheimer's disease. Science. 1988 Aug 26;241(4869):1080–1084. [PubMed]
  • Bahmanyar S, Higgins GA, Goldgaber D, Lewis DA, Morrison JH, Wilson MC, Shankar SK, Gajdusek DC. Localization of amyloid beta protein messenger RNA in brains from patients with Alzheimer's disease. Science. 1987 Jul 3;237(4810):77–80. [PubMed]
  • Schubert D, LaCorbiere M, Saitoh T, Cole G. Characterization of an amyloid beta precursor protein that binds heparin and contains tyrosine sulfate. Proc Natl Acad Sci U S A. 1989 Mar;86(6):2066–2069. [PMC free article] [PubMed]
  • Weidemann A, König G, Bunke D, Fischer P, Salbaum JM, Masters CL, Beyreuther K. Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein. Cell. 1989 Apr 7;57(1):115–126. [PubMed]
  • Takio K, Hasegawa M, Titani K, Ihara Y. Identification of beta protein precursor in newborn rat brain. Biochem Biophys Res Commun. 1989 May 15;160(3):1296–1301. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...