Sequencing of exons 16 and 17 of the β-amyloid precursor protein gene reveals the β-amyloid sequence to be normal in cases of the parkinson dementia complex of guam

  • M. -C. Chartier Harlin
  • F. Crawford
  • D. P. Perl
  • J. Steele
  • J. Hardy
Short Communication

Summary

Exons 16 and 17 of the β-amyloid precursor protein gene has been sequenced in individuals with the amyotropic lateral sclerosis/Parkinson's dementia complex of Guam to test the hypothesis that this disease is an allelic variant of Alzheimer's disease and to test whether sequence differences within β-amyloid in this population contributes to the non-deposition of this peptide in the disorder. The sequence was normal.

Keywords

β-amyloid APP amyotrophic lateral sclerosis Parkinson's disease Guam genetics Alzheimer's disease 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Chartier Harlin MC, Crawford F, Hamandi K, Mullan M, Goate A, Backhovens H, Martin JJ, Van Broeckhoven C (1991) Screening for the β-amyloid precursor protein mutation (APP:Val→Ile) in extended pedigrees with early onset Alzheimer's disease. Neurosci Lett 129: 134–135CrossRefPubMedGoogle Scholar
  2. Chartier Harlin MC, 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 β-amyloid precursor protein gene. Nature 353: 844–846CrossRefPubMedGoogle Scholar
  3. Gentleman SM, Perl D, Allsop D, Clinton J, Royston MC, Roberts GW (1991) Beta (A4)-amyloid protein and parkinsonian dementia complex of Guam. Lancet 337: 55–56CrossRefGoogle Scholar
  4. Goate A, Chartier Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, et al (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349: 704–706CrossRefPubMedGoogle Scholar
  5. Goldfarb LG, Korczyn AD, Brown P, Chapman J, Gajdusek DC (1990a) Mutation in codon 200 of scrapie amyloid precursor protein gene linked to Creutzfeldt-Jakob disease in Sephardic jews of Libyan and non-Libyan origin. Lancet 336: 637–638CrossRefGoogle Scholar
  6. Goldfarb LG, Mitrova E, Brown P, Toh BH, Gajdusek DC (1990b) Mutation in codon 200 of scrapie amyloid precursor gene in two clusters of Creutzfeldt-Jakob disease in Slovakia. Lancet 336: 514–515CrossRefGoogle Scholar
  7. Hardy J, Mullan M, Chartier Harlin MC, Brown J, Goate A, Rossor M, Collinge J, Roberts G, Luthert P, Lantos P, Naruse S, Kaneko K, Tsuji S, Miyatake T, Shimizu T, Kojima T, Nakano I, Yoshioka K, Sakaki Y, Miki T, Katsuya T, Ogihara T, Roses A, Pericak-Vance M, Haan J, Roos R, Lucotte G, Favid F (1991) Molecular classification of Alzheimer's disease. Lancet 337: 1342–1343Google Scholar
  8. Hsiao K, Meiner Z, Kahana E, Cass C, Kahana I, Avrahami D, Scarlato G, Abramsky O, Prusiner SB, Gabizon R (1990) Mutation of the prion protein in Libyan Jews with Creuzfeldt-Jakob disease. N Engl J Med 324: 1091–1097Google Scholar
  9. Murrell J, Farlow M, Ghetti B, Benson M (1991) A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science 254: 97–99PubMedGoogle Scholar
  10. Naruse S, Igarashi S, Kobayashi H, Aoki K, Inuzuka T, Kaneko K, Shimizu T, Iihara K, Kojima T, Miyatake T, Tsuji S (1991) Mis-sense mutation Val→Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease. Lancet 337: 978–979CrossRefGoogle Scholar
  11. Shankar SK, Yanagihara R, Garruto RM, Grundke Iqbal I, Kosik KS, Gajdusek DC (1989) Immunocytochemical characterization of neurofibrillary tangles in amyotrophic lateral sclerosis and parkinsonism-dementia of Guam. Ann Neurol 25: 146–151CrossRefPubMedGoogle Scholar
  12. Siddique T, Figlewicz DA, Pericak-Vance M, Haines JL, Rouleau G, Jeffers AJ, Sapp P, Hung WY, Bebout J, McKenna-Yasek D, Deng G, Horvitz HR, Gusella JF, Brown RH, Roses AD (1991) Linkage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity. N Engl J Med 324: 1381–1384PubMedGoogle Scholar
  13. St George Hyslop PH, Haines JL, Farrer LA, Polinsky R, Van Broeckhoven C, Goate A, McLachlan DR, Orr H, Bruni AC, Sorbi S, et al (1990) Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder. FAD Collaborative Study Group. Nature 347: 194–197Google Scholar
  14. Steele JC, Guzman T (1987) Observations about amyotrophic lateral sclerosis and the parkinsonism-dementia complex of Guam with regard to epidemiology and etiology. Can J Neurol Sci 14: 358–362PubMedGoogle Scholar
  15. Yoshioka K, Miki T, Katsuya T, Ogihara T, Sakaki Y (1991) The717Val→Ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups. Biochem Biophys Res Commun 178: 1141–1146CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • M. -C. Chartier Harlin
    • 1
  • F. Crawford
    • 1
  • D. P. Perl
    • 2
  • J. Steele
    • 3
  • J. Hardy
    • 1
  1. 1.Alzheimer's Disease Research Group, Departments of Biochemistry and Molecular GeneticsSt. Mary's Hospital Medicial SchoolLondonUK
  2. 2.Neuropathology DivisionMt. Sinai Medical CenterNew YorkU.S.A.
  3. 3.Guam Memorial HospitalAganaGuam

Personalised recommendations