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Hemorrhage is uncommon in new Alzheimer family with Flemish amyloid precursor protein mutation

W S Brooks1, J B J Kwok, G M Halliday

  • 1Prince of Wales Medical Research Institute, University of New South Wales, Barker Street, Randwick, Sydney, NSW 2031, Australia. w.brooks@unsw.edu.au

Neurology
|November 10, 2004
PubMed
Abstract

Insights

The Flemish mutation (APP Ala692Gly) in the amyloid precursor protein gene causes familial Alzheimer disease and cerebral hemorrhage. This British family showed dementia, with hemorrhage less frequent than in other families with this mutation.

Area of Science:

  • Genetics
  • Neurology
  • Molecular Biology

Background:

  • Mutations in the amyloid precursor protein (APP) gene are linked to familial Alzheimer disease (AD).
  • Some APP gene mutations within the Abeta-coding sequence are associated with recurrent cerebral hemorrhage.
  • The APPAla692Gly (Flemish) mutation was previously identified in a family with hemorrhagic stroke and/or dementia.

Observation:

  • This study investigated a British family with the Flemish APP mutation.
  • Clinical, neuropathologic, and genetic data were collected from affected and unaffected individuals.
  • Neuropathologic examination was performed on one affected case.

Findings:

  • Presenile dementia consistent with dominant inheritance was observed.
  • The APP692 mutation was present in all affected individuals and absent in unaffected individuals.
  • The proband experienced cerebral hemorrhage, an infrequent complication in this family.

Implications:

  • This research expands the number of families identified with APP gene mutations in the coding region.
  • Cerebral hemorrhage appears to be a less frequent complication in this family compared to previously reported cases with the same mutation.
  • Understanding APP mutations contributes to the diagnosis and management of familial Alzheimer disease and related cerebrovascular disorders.

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