AMYLOID ANGIOPATHY IN A VOLGA GERMAN FAMILY WITH ALZHEIMERS-DISEASE AND A PRESENILIN-2 MUTATION ((NI)-I-141)

We report the neuropathological features in 6 members of a Volga Germa n family with autosomal dominant Alzheimer's disease linked to chromos ome 1 who had a presenilin-2 mutation ((NI)-I-141). The most significa nt feature in this family was the presence of severe or moderately sev ere amyloid angiopathy in five family members with clinical dementia. The index case with the presenilin-2 mutation had late-onset dementia at age 73 years, died of an acute intracerebral hemorrhage, and pathol ogically showed severe amyloid angiopathy but only rare neuritic senil e plaques and neurofibrillary tangles. That she was apolipoprotein E e psilon 2/3 heterozygous suggests that the epsilon 2 allele may have ex erted a selective protective effect resulting in late onset relatively mild Alzheimer's disease despite severe amyloid angiopathy, This fami ly emphasizes the need for more investigation into the role of preseni lin mutations in amyloid deposition, especially in the cerebral vascul ature, and the role of these changes in clinical dementia.