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

[hereditary cerebral hemorrhage with amyloidosis]

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 APP 692 Ala -->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 APP 692 mutation . The neuropathological findings support the diagnosis of AD . Leptomeningial and parenchymal vessels showed extensive deposition of Abeta amyloid protein . Numerous senile plaques consisted of large Abeta amyloid cores , often measuring more than 30 microm 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 APP 692 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 APP 717 mutations causing familial , presenile AD and in patients with the APP 693 mutation causing HCHWA-D .