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PMID: 8644866 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Predominant deposition of amyloid-beta 42(43) in plaques in cases of Alzheimer's disease and hereditary cerebral hemorrhage associated with mutations in the amyloid precursor protein gene.

The American journal of pathology ·Vol. 148 ·No. 4 ·1996-04-00 ·Pages 1257-66

Mann DM, Iwatsubo T, Ihara Y, Cairns NJ, Lantos PL, Bogdanovic N, Lannfelt L, Winblad B, Maat-Schieman ML, Rossor MN

Abstract

Amyloid (A beta) deposition was investigated in cases of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis, Dutch type, due to mutations in the amyloid precursor protein (APP) gene using the end-specific monoclonal antibodies BA27 and BC05 that recognize A beta 40 or A beta 42(43), respectively. In cases of APP717 mutation the predominant A beta species within plaques terminate at A beta 42(43) with relatively little A beta 40 being present. The total amount of A beta deposited as A beta 42(43) is significantly greater than in sporadic Alzheimer's disease, consistent with the suggestion that this mutation might influence the processing of APP so as to produce more of the highly aggregatable form, A beta 1-42. In cases of APP670/671 mutation the major peptide in plaques is also A beta 42(43), although the proportion of plaques containing A beta 40, and the total A beta load is similar to that in sporadic Alzheimer's disease. As in sporadic Alzheimer's disease, the vascular amyloid in APP670/671 and APP717 and in cases of hereditary cerebral hemorrhage with amyloidosis, Dutch type is predominantly A beta 40 in this latter disorder, however, parenchymal deposits are exclusively A beta 42(43). Although the various APP mutations may influence the type, quantity, and location of A beta deposited, the predominant, and possibly the initial, species deposited in the brain parenchyma is A beta 42(43).

MeSH Terms
Adult Aged Aged, 80 and over Alzheimer Disease/genetics,metabolism,pathology Amino Acid Sequence/genetics Amyloid beta-Peptides/metabolism Amyloid beta-Protein Precursor/genetics,metabolism Cerebral Hemorrhage/genetics,metabolism,pathology Female Humans Immunohistochemistry Male Middle Aged Mutation Neurofibrillary Tangles/genetics,metabolism,pathology
Chemicals
Amyloid beta-Peptides Amyloid beta-Protein Precursor
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Mann D M
Department of Pathological Sciences, University of Manchester, United Kingdom.
Iwatsubo T
Ihara Y
Cairns N J
Lantos P L
Bogdanovic N
Lannfelt L
Winblad B
Maat-Schieman M L
Rossor M N
References (44)
44 references, click to expand
  1. Screening of the mis-sense mutation producing the 717Val-->Ile substitution in the amyloid precursor protein in Japanese familial and sporadic Alzheimer's disease.
    J Neurol Sci. 1993 Jul;117(1-2):12-5 PMID: 8410047
  2. Microglial cells and amyloid beta protein (A beta) deposition; association with A beta 40-containing plaques.
    Acta Neuropathol. 1995;90(5):472-7 PMID: 8560980
  3. Clinical comparison of Alzheimer's disease in pedigrees with the codon 717 Val-->Ile mutation in the amyloid precursor protein gene.
    Neurobiol Aging. 1993 Sep-Oct;14(5):407-19 PMID: 8247223
  4. 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 PMID: 8248178
  5. Chemical characterization of A beta 17-42 peptide, a component of diffuse amyloid deposits of Alzheimer disease.
    J Biol Chem. 1994 Apr 15;269(15):10987-90 PMID: 8157623
  6. Development of a monoclonal antibody specific for the COOH-terminal of beta-amyloid 1-42 and its immunohistochemical reactivity in Alzheimer's disease and related disorders.
    Am J Pathol. 1994 May;144(5):1082-8 PMID: 8178931
  7. Soluble amyloid beta-protein is a marker of Alzheimer amyloid in brain but not in cerebrospinal fluid.
    Biochem Biophys Res Commun. 1994 May 16;200(3):1598-603 PMID: 8185615
  8. An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants.
    Science. 1994 May 27;264(5163):1336-40 PMID: 8191290
  9. Normal and abnormal biology of the beta-amyloid precursor protein.
    Annu Rev Neurosci. 1994;17:489-517 PMID: 8210185
  10. Altered cleavage and secretion of a recombinant beta-APP bearing the Swedish familial Alzheimer's disease mutation.
    Nat Genet. 1994 Mar;6(3):251-5 PMID: 8012386
  11. Amyloid precursor protein mutation causes Alzheimer's disease in a Swedish family.
    Neurosci Lett. 1994 Feb 28;168(1-2):254-6 PMID: 8028788
  12. Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43).
    Neuron. 1994 Jul;13(1):45-53 PMID: 8043280
  13. Relative abundance of Alzheimer A beta amyloid peptide variants in Alzheimer disease and normal aging.
    Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8378-82 PMID: 8078890
  14. Lewy bodies in the brain of two members of a family with the 717 (Val to Ile) mutation of the amyloid precursor protein gene.
    Neurosci Lett. 1994 May 19;172(1-2):77-9 PMID: 8084541
  15. Increased beta-amyloid release and levels of amyloid precursor protein (APP) in fibroblast cell lines from family members with the Swedish Alzheimer's disease APP670/671 mutation.
    FEBS Lett. 1994 Nov 14;354(3):274-8 PMID: 7957938
  16. APP717 missense mutation affects the ratio of amyloid beta protein species (A beta 1-42/43 and a beta 1-40) in familial Alzheimer's disease brain.
    J Biol Chem. 1994 Dec 30;269(52):32721-4 PMID: 7806491
  17. Hereditary cerebral hemorrhage with amyloidosis (Dutch): a model for congophilic plaque formation without neurofibrillary pathology.
    Acta Neuropathol. 1994;88(4):371-8 PMID: 7839831
  18. Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein.
    Nature. 1995 Feb 9;373(6514):523-7 PMID: 7845465
  19. Polyclonals to beta-amyloid(1-42) identify most plaque and vascular deposits in Alzheimer cortex, but not striatum.
    Brain Res. 1994 Dec 19;667(1):138-42 PMID: 7895077
  20. Amyloid beta protein (A beta) deposition: A beta 42(43) precedes A beta 40 in Down syndrome.
    Ann Neurol. 1995 Mar;37(3):294-9 PMID: 7695229
  21. Amyloid beta protein (A beta) in Alzheimer's disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at A beta 40 or A beta 42(43).
    J Biol Chem. 1995 Mar 31;270(13):7013-6 PMID: 7706234
  22. Amyloid beta protein deposition in normal aging has the same characteristics as that in Alzheimer's disease. Predominance of A beta 42(43) and association of A beta 40 with cored plaques.
    Am J Pathol. 1996 Jan;148(1):259-65 PMID: 8546214
  23. 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):885-90 PMID: 6375662
  24. Amyloid plaque core protein in Alzheimer disease and Down syndrome.
    Proc Natl Acad Sci U S A. 1985 Jun;82(12):4245-9 PMID: 3159021
  25. Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease.
    Proc Natl Acad Sci U S A. 1987 Aug;84(16):5991-4 PMID: 3475718
  26. Differences between vascular and plaque core amyloid in Alzheimer's disease.
    J Neurochem. 1988 Aug;51(2):648-51 PMID: 3292706
  27. Protein chemical and immunocytochemical studies of meningovascular beta-amyloid protein in Alzheimer's disease and normal aging.
    Brain Res. 1988 Nov 22;474(1):100-11 PMID: 3214703
  28. Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type.
    Science. 1990 Jun 1;248(4959):1124-6 PMID: 2111584
  29. 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 PMID: 1678058
  30. Familial Alzheimer's disease with the amyloid precursor protein position 717 mutation and sporadic Alzheimer's disease have the same cytoskeletal pathology.
    Neurosci Lett. 1992 Mar 30;137(2):221-4 PMID: 1584463
  31. Pathological changes in the brain of a patient with familial Alzheimer's disease having a missense mutation at codon 717 in the amyloid precursor protein gene.
    Neurosci Lett. 1992 Mar 30;137(2):225-8 PMID: 1584464
  32. Spectrum of amyloid beta-protein immunoreactivity in hereditary Alzheimer disease with a guanine to thymine missense change at position 1924 of the APP gene.
    Brain Res. 1992 Jan 31;571(1):133-9 PMID: 1611485
  33. Amyloid beta-peptide is produced by cultured cells during normal metabolism.
    Nature. 1992 Sep 24;359(6393):322-5 PMID: 1383826
  34. Production of the Alzheimer amyloid beta protein by normal proteolytic processing.
    Science. 1992 Oct 2;258(5079):126-9 PMID: 1439760
  35. Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production.
    Nature. 1992 Dec 17;360(6405):672-4 PMID: 1465129
  36. Tau pathology in a case of familial Alzheimer's disease with a valine to glycine mutation at position 717 in the amyloid precursor protein.
    Neurosci Lett. 1992 Oct 12;145(2):178-80 PMID: 1465214
  37. Secretion of beta-amyloid precursor protein cleaved at the amino terminus of the beta-amyloid peptide.
    Nature. 1993 Jan 21;361(6409):260-3 PMID: 7678698
  38. Release of excess amyloid beta protein from a mutant amyloid beta protein precursor.
    Science. 1993 Jan 22;259(5094):514-6 PMID: 8424174
  39. Structural alterations in the peptide backbone of beta-amyloid core protein may account for its deposition and stability in Alzheimer's disease.
    J Biol Chem. 1993 Feb 15;268(5):3072-83 PMID: 8428986
  40. Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer's disease.
    Arch Biochem Biophys. 1993 Feb 15;301(1):41-52 PMID: 8442665
  41. Beta A4 protein deposition in familial Alzheimer's disease with the mutation in codon 717 of the beta A4 amyloid precursor protein gene and sporadic Alzheimer's disease.
    Neurosci Lett. 1993 Jan 12;149(2):137-40 PMID: 8474686
  42. The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease.
    Biochemistry. 1993 May 11;32(18):4693-7 PMID: 8490014
  43. 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 PMID: 1303239
  44. Characterization of beta-amyloid peptide from human cerebrospinal fluid.
    J Neurochem. 1993 Nov;61(5):1965-8 PMID: 8229004
Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1996-04-00
Pages
1257-66
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1861527
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source PMC Full Text View journal details
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