A novel APP mutation (D678H) in a Taiwanese patient exhibiting dementia and cerebral microvasculopathy.

We report a novel missense mutation, D678H, in the APP gene in a Taiwanese patient who had progressive cognitive decline beginning in middle age. Brain MRI showed leukoencephalopathy, cortical microhemorrhages and focal superficial cortical hemosiderosis, which are consistent with cerebral amyloid angiopathy. A phenotype of combined dementia and cerebral microvasculopathy suggested concurrent increases in brain parenchymal and cerebrovascular beta-amyloid peptide (Aβ) deposition in this patient. The promotion of Aβ aggregation has been postulated to underlie the pathogenic mechanism of the mutation.