Skip to main content
SpringerLink
Log in

Molecular biology of Alzheimer's amyloid—Dutch variant

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D) (or familial cerebral amyloid angiopathy) and familial Alzheimer's disease (FAD) share several properties. Both are autosomal dominant forms of cerebral amyloidosis characterized by β-amyloid (Aβ) deposition. In HCHWA-D the Aβ is predominantly found in blood vessels and in early parenchymal plaques, whereas in AD parenchymal Aβ deposits in the form of senile plaques and neurofibrillary tangles are a more prominent finding. Point mutations in the amyloid precursor protein (APP) have recently been described, in both conditions. A G to C transversion at codon 618 (extracellular portion of APP695), producing a single amino acid substitution of glutamine instead of glutamine acid, occurs in HCHWA-D; whereas mutations at codon 642 in the intramembrane region of APP695 (phenylalanine, isoleucine, or glycine instead of valine) are associated with early onset FAD. This suggests that the site of particular mutations in the APP gene and the type of amino acid substitution in the APP holoprotein are more important in determining clincopathological phenotype and age at which Aβ is deposited. Thus FAD and HCHWA-D can be regarded as two sides of the same coin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alzheimer A. (1907) Uber eine eigenartige Erkrankung der Hirnrinde.Allg. Z. Psychiat Psych. Gerichte. Med. 64, 146–148.

    Google Scholar 

  • Bakker E., van Broeckhoven C., Haan J., Voorhoeve E., van Hul W., Levy E., Lieberburg I., Carman M. D., van Ommen G. J. B., Frangione B., and Roos R. A. C. (1991) DNA diagnosis for hereditary cerebral hemorrhage with amyloidosis (Dutch type).Am. J. Hum. Genet. 9, 518–521.

    Google Scholar 

  • Barrow C. J. and Zagorski M. G. (1991) Solution structures of β peptide and its constituent frag-ments: relation to amyloid deposition.Science 253, 179–182.

    Article  PubMed  CAS  Google Scholar 

  • Benedikz E., Blondal H., and Gudmundsson G. (1990) Skin deposits in hereditary cystatin c amyloidosis.Virchows Archiv A 417, 325–331.

    Article  CAS  Google Scholar 

  • Beyreuther K. and Masters C. L. (1991) Amyloid precursor protein (APP) and βA4 amyloid in the etiology of Alzheimer's disease: Precursor-product relationships in the derangement of neuronal function.Brain Pathol. 1, 241–251.

    Article  PubMed  CAS  Google Scholar 

  • Castaño E., Ghiso J., Prelli F., Gorevic P., Migheli A., and Frangione B. (1986) In vitro formation of amyloid fibrils from two synthetic peptides of different lengths homologous to Alzheimer's disease β-protein.Biochem. Biophys. Res. Commun. 141, 782–789.

    Article  PubMed  Google Scholar 

  • Castaño E. M. and Frangione B. (1991) Alzheimer's disease from the perspective of the systemic and localized forms of amyloidosis.Brain Pathol. 1, 263–271.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Coria F., Castaño E. M., and Frangione B. (1987) Brain amyloid in normal aging and cerebral amyloid angiopathy is antigenically related to Alzheimer's disease beta-protein.Am. J. Pathol. 129, 422–429.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Dyrks T., Weidemann A., Multhaup G., Salbaum J. M., Lemaire H.-G., Kang J., Müller-Hill B., Masters C. L., and Beyreuther K. (1988) Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease.EMBO J. 7, 949–957.

    PubMed  CAS  Google Scholar 

  • Esch F. S., Keim P. S., Beattie E. C., Blacker R. W., Culwell A. K., Oltersdorf T., McClure D., and Ward P. J. (1990) Cleavage of amyloid β peptide during constitutive processing of its precursor.Science 248, 1122–1124.

    Article  PubMed  CAS  Google Scholar 

  • Estus S., Golde T. E., Kunishita T., Blades D., Lowery D., Eisen M., Usiak M., Qu X., Tabira T., Greenberg B. D., and Younkin S. G. (1992) Potentially amyloid-ogenic carboxyl-terminal derivates of the amyloid protein precursor.Science 255, 726–728.

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Madrid I., Levy E., Marder K., and Frangione B. (1991) Codon 618 variant of Alzheimer amyloid gene associated with inherited cerebral hemorrhage.Ann. Neurol. 30, 730–733.

    Article  PubMed  CAS  Google Scholar 

  • Gandy S. E., Bhasin R., Ramabhadran T. V., Koo E. H., Price D. L., Goldgaber D., and Greengard P. (1992) Alzheimer β/A4-amyloid precursor protein: evidence for putative amyloidogenic fragment.J. Neurochem. 58, 383–386.

    Article  PubMed  CAS  Google Scholar 

  • Ghiso J., Jensson O., and Frangione B. (1986) Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of gamma-trace basic protein (cystatin c).Proc. Natl. Acad. Sci. USA 83, 2974–2978.

    Article  PubMed  CAS  Google Scholar 

  • Ghiso J. and Frangione B. (1992) Alternative processing pathway of Alzheimer's amyloid precursor protein in cerebral vessel walls (unpublished observations).

  • Giaccone G., Tagliavini F., Linoli G., Bouras C., Frigerior L., Frangione B., and Bugiani O. (1989) Down patients: extracellular preamyloid deposits precede neuritic degeneration and senile plaques.Neurosci. Lett. 97, 232–238.

    Article  PubMed  CAS  Google Scholar 

  • Glenner G. G., Henry J. H., and Fujihara S. (1981) Congophilic angiopathy in the pathogenesis of Alzheimer's degeneration.Ann. Pathol. 1, 120–129.

    PubMed  CAS  Google Scholar 

  • Glenner G. G. and Wong C. W. (1984) Alzheimer's disease and Down's syndrome:sharing of 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., and 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 

  • Goate A., Owen M. J., James L. A., Mullan M. J., Rossor M. N., Haynes A. R., Farrall M., Lai L. Y. C. Roques P., Williamson R., and Hardy J. A. (1989) Predisposing locus for Alzheimer's disease on chromosome 21.Lancet 1, 352–355.

    Article  PubMed  CAS  Google Scholar 

  • Golde T. E., Estus S., Usiak M., Younkin L. H., and Younkin S. G. (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 

  • Golde T. E., Estus S., Younkin L. H., Selkoe D. J., and Younkin S. G. (1992) Processing of the amyloid protein precursor to potentially amyloidogenic derivatives.Science 255, 728–730.

    Article  PubMed  CAS  Google Scholar 

  • Goldgaber D., Lerman M. J., McBride O. W., Saffiotti U., and Gajdusek D. C. (1987) Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease.Science 235, 877–880.

    Article  PubMed  CAS  Google Scholar 

  • Grubb A. and Lofberg H. (1985) Human gamma trace structure, function and clinical use of concentration measurements.Scand. J. Clin. Lab. Invest. 45 (Suppl. 177), 7–13.

    CAS  Google Scholar 

  • Gudmundsson G., Hallgrimsson J., Jonasson T. A., and Bjarnason O. (1972) Hereditary cerebral hemorrhage with amyloidosis.Brain 95, 387–404.

    Article  PubMed  CAS  Google Scholar 

  • Haan J., Roos R. A. C., Briet P. E., Herpers M. H. J. M. Luyendijk W., Bots G. T. A. M., and the Research Group on Hereditary Cerebral Amyloid-Angiopathy (1989) Hereditary cerebral hemorrhage with amyloidosis—Dutch type.Clin. Neurol. Neurosurg. 91, 285–290.

    Article  PubMed  CAS  Google Scholar 

  • Haan J., Lauser J. B. K., Zijderveld L., vander Does I. G. F., and Roos R. A. C. (1990) Dementia in hereditary cerebral hemorrhage with amyloidosis-Dutch type.Arch. Neurol. 47, 965–967.

    PubMed  CAS  Google Scholar 

  • Haan J., Hardy J. A., and Roos R. A. C. (1991) Hereditary cerebral hemorrhage with amyloidosis-Dutch type: its importance for Alzheimer research.Trends in Neuroscience 14(No. 6), 231–234.

    Article  CAS  Google Scholar 

  • Hilbich C., Kisters-Weike B., Reed J., Masters C. L., and Beyreuther K. (1991) Aggregation and secondary structure of synthetic amyloid βA4 peptides of Alzheimer's disease.J. Mol. Biol. 218, 149–163.

    Article  PubMed  CAS  Google Scholar 

  • Jacobsen J. S., Muerkel H. A., Blume A. J., and Vitek M. P. (1991) A novel species specific RNA related to alternatively spliced amyloid precursor protein mRNAs.Neurobiol. Aging 12, 575–583.

    Article  PubMed  CAS  Google Scholar 

  • Joachim C. L., Morris J., and Selkoe D. J. (1986) Autopsy neuropathology in 76 cases of clinically diagnosed Alzheimer's disease.Neurology 36 (Suppl. 1), 226.

    Google Scholar 

  • Kang J. Lemaire H. G., Unterbeck A., Salbaum J. M., Masters C. L., Grzeschik K. H., Malthaup G., Beyreuther K., and Müller-Hill B. (1987) The precursor of Alzheimer's disease amyloid A4 protein resembles cell surface receptor.Nature 325, 733–736.

    Article  PubMed  CAS  Google Scholar 

  • Kirschner D. A., Inouye H., Duffy L., Sinclair A., Lind M., and Selkoe D. J. (1987) Synthetic peptide homologous to β protein from Alzheimer disease forms amyloid-like fibrils in vitro.Proc. Natl. Acad. Sci. USA 84, 6953–6957.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Lemaire H. G., Salbaum J. M., Multhaup G., Kang J., Bayney R. M., Unterbeck A., Beyreuther K., and Müller-Hill B. (1989) The Pre A4695 precursor protein of Alzheimer's disease A4 amyloid is encoded by 16 exons.Nucleic Acids Res. 17, 517–522.

    Article  PubMed  CAS  Google Scholar 

  • Levy E., Lopez-Otin C., Ghiso J., Geltner D., and Frangione B. (1989) Stroke in Icelandic patients with hereditary amyloid angiopathy is related to a mutation in the cystatin C gene, an inhibitor of cysteine proteases.J. Exp. Med. 169, 1771–1778.

    Article  PubMed  CAS  Google Scholar 

  • Levy E., Carman M. D., Fernandez-Madrid I. J., Power M. D., Lieberburg I., van Duinen S. G., Bots G. Th. A. M., Luyendijk W., and Frangione B. (1990) Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type.Science 248, 1124–1126.

    Article  PubMed  CAS  Google Scholar 

  • Lucotte G., Berriche S., and David F. (1991) Alzheimer's mutation.Nature 351, 530.

    Article  PubMed  CAS  Google Scholar 

  • Luyendijk W., Bots G. T. A. M., Vegter-van der Vlis M., Went L. N., and Frangione B. (1988) Hereditary cerebral haemorrhage caused by cortical amyloid angiopathy.J. Neurol. Sci. 85, 267–280.

    Article  PubMed  CAS  Google Scholar 

  • Mann D. M. A. (1989) Cerebral amyloidosis, aging and Alzheimer's disease: a contribution from studies on Down's syndrome.Neurobiol. Aging 10, 397–399.

    Article  PubMed  CAS  Google Scholar 

  • Masters C. L., Simms G., Weinman N. A., Multhaup G., McDonald B. L., and Beyreuther K. (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome.Proc. Natl. Acad. Sci. USA 82, 4245–4249.

    Article  PubMed  CAS  Google Scholar 

  • Motte J. and Williams R. S. (1989) Age-related changes in the density and morphology of plaques and neurofibrillary tangles in Down syndrome brain.Acta Neuropathol. 77, 535–546.

    Article  PubMed  CAS  Google Scholar 

  • Murrell J., Farlow M., Ghetti B., and Benson M. D. (1991) A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease.Science 254, 97–99.

    Article  PubMed  CAS  Google Scholar 

  • Naruse S., Igarashi S., Kobayashi H., Aoki K., Inuzuka T., Kaneko K., Shimizu T., Iihara K., Kojima T., Miyatake T., and Tsuji S. (1991) Mis-sense mutation Val→Ile in exon 17 of amyloid precursor gene in Japanese familial Alzheimer's disease.Lancet 337, 978,979.

    Article  PubMed  CAS  Google Scholar 

  • Nordstedt C., Gandy S. E., Alafuzoff I., Caporaso G. L., Iverfeldt K., Grebb J. A., Winblad B. and Greengard P. (1991) Alzheimer/A4 amyloid precursor protein in human brain: aging associated increases in holoprotein and in a proteolytic fragment.Proc. Natl. Acad. Sci. USA 88, 8910–8914.

    Article  PubMed  CAS  Google Scholar 

  • Oltersdorf T., Ward P. J., Henrikkson T., Beattie E. C., Neve R., Lieberburg I., and Fritz L. C. (1989) The Alzheimer amyloid precursor protein: Identification of a stable intermediate in the biosynthetic/degradative pathway.J. Biol. Chem. 265, 4492–4497.

    Google Scholar 

  • Palsdottir A., Abrahamson M., Thorsteinsson L., Arnason A., Olafsson I., Grubb A., and Jensson O. (1988) Mutation in cystatin C gene causes hereditary brain haemorrhage.Lancet 2, 603,604.

    Article  PubMed  CAS  Google Scholar 

  • Pericak-Vance M., Yamaoka L. H., Haynes C. S., Speer M. C., Haines J. L., Gaskell P. C., Hung W.-Y., Clark C. M., Heyman A. L., Trofatter J. A., Eisenmenber J. P., Gilbert J. R., Lee J. E., Alberts M. J., Dawson D. V., Bartlett R. J., Earl N. L., Siddique T., Vance J. M., Conneally P. M., and Roses A. D. (1988) Genetic linkage studies in Alzheimer's disease families.Exp. Neurol. 102, 271–279.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Prelli F., Castano E. M., van Duinen S. G., Bots G. T., Luyendijk W., and Frangione B. (1988) Different processing of Alzheimer's beta-protein precursor in the vessel wall of patients with hereditary cerebral hemorrhage with amyloidosis, Dutch type.Biochem. Biophys. Res. Commun. 151, 1150–1155.

    Article  PubMed  CAS  Google Scholar 

  • Prelli F., Levy E., van Duinen S. G., Bots G. Th. A. M., Luyendijk W., and Frangione B. (1990) Expression of a normal and variant Alzheimer's beta-protein gene in amyloid of hereditary cerebral hemorrhage, Dutch type, DNA and protein diagnostic assays.Biochem. Biophys. Res. Commun. 170, 301–307.

    Article  PubMed  CAS  Google Scholar 

  • Prelli F., Castano E. M., Glenner G. G., and Frangione B. (1988) Differences between vascular and plaque core amyloid in Alzheimer's disease.J. Neurochem. 51, 648–651.

    Article  PubMed  CAS  Google Scholar 

  • Probst A., Langui D., and Ulrich J. (1991) Alzheimer's disease: a description of the structural lesions.Brain Pathol. 1, 229–239.

    Article  PubMed  CAS  Google Scholar 

  • Robakis N. K., Wisniewski H. M., Jenkins E. C., Devine-Gage E. A., Houck G. E., Yao X.-L., Ramakrishna N., Wolfe G., Silverman W. P., and Brown W. T. (1987) Chromosome 21q21 sublocalization of gene encoding β-amyloid peptide in cerebral vessels and neuritic (senile) plaques of people with Alzheimer's disease and Down syndrome.Lancet 1, 384,385.

    Article  PubMed  CAS  Google Scholar 

  • Rumble B., Retallack R., Hilbich C., Simms G., Multhaup G., Martins R., Hockey A., Montgomery P., Beyreuther K., and Masters C. L. (1989) Amyloid A4 protein and its precursor in Down's syndrome and Alzheimer's disease.N. Engl. J. Med. 320, 1446–1452.

    PubMed  CAS  Google Scholar 

  • Schellenberg G.D., Anderson L., O'Dahl S., Wisjman E. M., Sadovnick A. D., Ball M. J., Larson E. B., Kukull W. A., Martin G. M., Roses A. D., and Bird T. D. (1991) APP717, APP693 and PRIP gene mutations are rare in Alzheimer's disease.Am. J. Hum. Genet. 49, 511–517.

    PubMed  CAS  Google Scholar 

  • Schellenberg G. D., Bird T. D., Wijsman E. M., Moore D. K., Boehnke M., Bryant E. M., Lampe T. H., Nochlin D., Sumi S. M., Deeb S. S., Beyreuther K., and Martin G. M. (1988) Absence of linkage of chromosome 21q21 markers to familial Alzheimer's disease.Science 241, 1507–1510.

    Article  PubMed  CAS  Google Scholar 

  • Selkoe D. J., Abraham C. R., Podlisny M. B., and Duffy L. K. (1986) Isolation of low-molecular-weight proteins from amyloid plaque fibers in Alzheimer's disease.J. Neurochem. 146, 1820–1834.

    Google Scholar 

  • Simchowicz T. (1911) Histologische studien über die senile demenz.Histologische und Histopatholoaische Arbeiten über die Grosshirnrinde (Nissl F. and Alzheimer A., eds.),4, 267–444.

  • Sisodia S. S., Koo E. H., Beyreuther K., Unterbeck A., and Price D. L. (1990) Evidence that amyloid protein in Alzheimer's disease is not derived by normal processing.Science 248, 492–495.

    Article  PubMed  CAS  Google Scholar 

  • St. George-Hyslop P. and Members of the FAD Collaborative Study Group (1990) Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder.Nature 347, 194–197.

    Article  PubMed  CAS  Google Scholar 

  • Tagliavini F., Ghiso J., Timmers W. F., Giaccone G., Bugiani O., and Frangione B. (1990) Coexistence of Alzheimer's amyloid precursor protein and amyloid protein in cerebral vessel walls.Lab. Invest. 62, 761–767.

    PubMed  CAS  Google Scholar 

  • Tanzi R. E., McClatchy A. I., Lamperti E. D., Villa-Kornaroff L., Gusella J. F., and Neve R. L. (1988) Protease inhibitor domain encoded by an amyloid precursor mRNA associated with Alzheimer's disease.Nature 331, 528–530.

    Article  PubMed  CAS  Google Scholar 

  • Tanzi R. E., Gusella J. F., Watkins P. C., Bruns G. A. P., St. George-Hyslop P., Van Keuren M. C., Patterson D., Pajan S., Kurnit D. M., and Neve R. L. (1987) Amyloid β-protein gene: cDNA, mRNA distribution and genetic linkage near the Alzheimer locus.Science 235, 880–884.

    Article  PubMed  CAS  Google Scholar 

  • Timmers W. F., Tagliavini F., Haan J., and Frangione B. (1990) Parenchymal preamyloid and amyloid deposits in the brains of patients with hereditary cerebral hemorrhage with amyloidosis Dutch type.Neurosci. Lett. 118, 223–226.

    Article  PubMed  CAS  Google Scholar 

  • Van Broeckhoven C., Haan J., Bakker F., Hardy J. A., Van Hul W., Wehnert A., Vegter-Van der Vlis M., and Roos R. A. C. (1990) Amyloid β protein precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch).Science 248, 1120–1122.

    Article  PubMed  Google Scholar 

  • van Duinen S. G., Castano E. M., Prelli F., Bots G. Th. A. M., Luyendijk W. and Frangione B. (1987) Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease.Proc. Natl. Acad. Sci. USA 8, 5991–5994.

    Article  Google Scholar 

  • Wang R., Meschia J. F., Lotter R. J., and Sisodia S. S. (1991) Secretion of the β/A4 amyloid precursor protein.J. Biol. Chem. 266, 16,960–16,964.

    CAS  Google Scholar 

  • Wattendorff A. R., Bots G. T. A. M., Went L. N., and Endtz L. J. (1982) Familial cerebral amyloid angiopathy presenting as recurrent cerebral hemorrhage.J. Neurol. Sci. 55, 121–135.

    Article  PubMed  CAS  Google Scholar 

  • Weidemann A., Konig G., Bunke D., Fischer P., Salbaum J. M., Masters C. L., and 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 

  • Wisniewski H. M., Bancher C., Barcikowska M., Wen G. Y., and Currie J. (1989) Spectrum of morphological appearance of amyloid deposits in Alzheimer's disease.Acta Neuropathol. 78, 337–347.

    Article  PubMed  CAS  Google Scholar 

  • Wisniewski K., Jervis G. A., Moretz R. C., and Wisniewski H. M. (1979) Alzheimer neurofibrillary tangles in diseases other than senile and presenile dementia.Ann. Neurol. 5, 228–294.

    Article  Google Scholar 

  • Wisniewski T., Ghiso J., and Frangione B. (1991) Peptides homologous to the amyloid protein of Alzheimer's disease containing a glutamine for glutamic acid substitution have accelerated amyloid fibril formation.Biochem. Biophys. Res. Commun. 179, 1247–1254.

    Article  PubMed  CAS  Google Scholar 

  • Wong C. W., Quaranta V., and Glenner G. G. (1985) Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are antigenically related.Proc. Natl. Acad. Sci. USA 82, 8729–8732.

    Article  PubMed  CAS  Google Scholar 

  • Yoshikai S., Sasaki H., Doh-ura K., Furuya H., and Sakaki Y. (1990) Genomic organization of the human amyloid-protein precursor gene.Gene 87, 257–263.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, New York University Medical Center, 550 First Avenue, 10016, New York, NY

    Thomas Wisniewski

  2. Department Pathology, New York University Medical Center, 550 First Avenue, 10016, New York, NY

    Thomas Wisniewski & Blas Frangione

Authors
  1. Thomas Wisniewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Blas Frangione
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wisniewski, T., Frangione, B. Molecular biology of Alzheimer's amyloid—Dutch variant. Mol Neurobiol 6, 75–86 (1992). https://doi.org/10.1007/BF02935567

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02935567

Index Entries

Search

Navigation