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Acta Neuropathologica

, Volume 96, Issue 3, pp 253–260 | Cite as

Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692Ala→Gly mutation

  • P. Cras
  • F. van Harskamp
  • L. Hendriks
  • C. Ceuterick
  • C. M. van Duijn
  • S. Z. Stefanko
  • A. Hofman
  • J. M. Kros
  • C. Van Broeckhoven
  • J. J. Martin
  • F. van Harskamp
Regular paper

Abstract

Mutations at codons 717 and 670/671 in the amyloid precursor protein (APP) are rare genetic causes of familial Alzheimer’s disease (AD). A mutation at codon 693 of APP has also been described as the genetic defect in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D). We have reported a APP692Ala→Gly (Flemish) mutation as a cause of intracerebral hemorrhage and presenile dementia diagnosed as probable AD in a Dutch family. We now describe the post-mortem examination of two demented patients with the APP692 mutation. The neuropathological findings support the diagnosis of AD. Leptomeningial and parenchymal vessels showed extensive deposition of Aβ amyloid protein. Numerous senile plaques consisted of large Aβ amyloid cores, often measuring more than 30 μm in diameter and were surrounded by a fine meshwork of dystrophic neurites. In addition, there were a large number of paired helical filaments in pyramidal neurons and dystrophic neurites. Our findings show that the APP692 mutation leads to morphological abnormalities that are similar to AD, but the morphology of senile plaques is clearly distinct from that described in sporadic and chromosome 14-linked AD patients, in patients with APP717 mutations causing familial, presenile AD and in patients with the APP693 mutation causing HCHWA-D.

Key words Congophilic angiopathy Amyloid precursor protein Dementia Neurofibrillary tangles Tau 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • P. Cras
    • 1
  • F. van Harskamp
    • 4
  • L. Hendriks
    • 2
  • C. Ceuterick
    • 1
  • C. M. van Duijn
    • 5
  • S. Z. Stefanko
    • 3
  • A. Hofman
    • 5
  • J. M. Kros
    • 3
  • C. Van Broeckhoven
    • 2
  • J. J. Martin
    • 1
  • F. van Harskamp
    • 5
  1. 1.Laboratory of Neuropathology, Born-Bunge Foundation, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium e-mail; cras@uia.ua.ac.be, Tel.: 32-3-820-2604, Fax: 32-3-820-2248BE
  2. 2.Laboratory of Neurogenetics, Flanders Interuniversity Institute of Biotechnology (VIB), Born Bunge Foundation, Department of Biochemistry, University of Antwerp, Wilrijk, BelgiumBE
  3. 3.Department of Pathology, Erasmus University, Rotterdam, The NetherlandsNL
  4. 4.Department of Neurology, Erasmus University, Rotterdam, The NetherlandsNL
  5. 5.Department of Epidemiology and Biostatistics, Erasmus University, Rotterdam, The NetherlandsNL

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