Background: Most mutations in the amyloid precursor protein (APP) gene have been associated with familial Alzheimer disease (AD); however, some mutations within the Abeta-coding sequence have been described in families with recurrent cerebral hemorrhage. The APPAla692Gly (Flemish) mutation was reported in a family in which affected members developed hemorrhagic stroke, progressive dementia, or both.
Objective: To describe clinical, neuropathologic, and genetic features of a family of British origin with the Flemish APP mutation.
Methods: Clinical features of the proband and two affected relatives were obtained by history, examination, and medical record review. Some information on deceased affected relatives was obtained by informant interview. Neuropathologic examination was carried out on one case. DNA studies were carried out on three affected and three unaffected individuals.
Results: Presenile dementia was present in a pattern consistent with dominant inheritance, with the APP692 mutation being found in all affecteds and no unaffecteds. The proband also had a cerebral hemorrhage, but was the only one of five affecteds to have this complication. Neuropathologic examination confirmed AD, congophilic angiopathy, and hemorrhagic infarction.
Conclusions: This expands the number of families reported with mutations in the coding region of the amyloid precursor protein gene. Cerebral hemorrhage appears to be less frequent in this family than in the previously reported Flemish pedigree with the same mutation.