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Hereditary cerebral hemorrhage with amyloidosis, Dutch type, caused by a mutation at codon 693 of the amyloid beta precursor protein gene, is characterized by amyloid beta deposition resulting in recurrent strokes and dementia. Recent data suggest that presenilin-1 may be biologically linked to cerebral amyloid beta deposition. The intronic presenilin-1 polymorphism published by Wragg and colleagues (1996) was analyzed in 65 carriers of the hereditary cerebral hemorrhage with amyloidosis, Dutch type, mutation. We found that the presenilin-1 genotype was not correlated with age at first stroke, number of recurrences, dementia, and age at death or with white matter hyperintensities and focal lesions on magnetic resonance images. From our data we conclude that amyloid beta deposition in this disease is most likely not influenced by presenilin-1.

Hereditary cerebral hemorrhage with amyloidosis-Dutch type is caused by a mutation at codon 693 of the beta amyloid precursor protein gene. The disease is clinically characterized by strokes and dementia. In addition to cerebral plaques, cerebral amyloid angiopathy is the pathological hallmark. We investigated the correlation between radiological (white matter hyperintensities and focal lesions on magnetic resonance images) and pathological lesions (cerebrovascular amyloid angiopathy and plaques) and the apolipoprotein E genotype in patients with the disease. Twenty-five patients were studied using magnetic resonance imaging, and brain tissue from 8 patients was studied histopathologically. Neither the white matter hyperintensity scores nor the number of focal lesions on magnetic resonance images were associated with the presence of an epsilon4 allele. Nor was a correlation found between the number and type of plaques and the apolipoprotein E genotype. All patients had severe amyloid angiopathy in all cortical areas investigated. This study showed that the apolipoprotein E genotype does not modulate amyloid-related structural lesions in hereditary cerebral hemorrhage with amyloidosis of the Dutch type.

In 31 symptomatic and 5 asymptomatic carriers of the amyloid precursor protein (APP) gene codon 693 mutation, 10 family members without mutation, and 5 carriers of the APP gene codon 692 mutation (3 with early-onset Alzheimer dementia, 2 with cerebral hemorrhage), a high frequency of the apolipoprotein E epsilon 4 allele was found. Age at onset, age at death, occurrence of dementia, and number of strokes did not differ between APP gene mutation carriers with or without epsilon 4 allele, showing that the clinical expression of these APP mutations is not influenced by the apolipoprotein E gene.