Faculty Bibliography

Hereditary cerebral hemorrhage with amyloidosis Dutch type (HCHWA-D) is characterized clinically by recurrent strokes and pathologically by deposition of amyloid beta (A beta) in cerebral vessel walls and, to a lesser extent, in the neuropil. Distinct from Alzheimer's disease, amyloid formation in HCHWA-D is not associated with neurofibrillary changes. Since a central issue in the pathophysiology of Alzheimer's disease and related conditions is the role of A beta in the neurodegenerative process, we investigated HCHWA-D brains for the presence of neuritic abnormalities using antibodies to ubiquitin and to phosphorylated neurofilaments. The study showed that amyloid deposits in the vessel walls and in the neuropil were surrounded by abnormal ubiquitinated neurites, suggesting that A beta deposition induces neuritic changes

Gerstmann-Straussler-Scheinker disease in the Indiana kindred is pathologically characterized by deposits of PrP-amyloid, neurofibrillary tangles and degenerating neurites. The aim of this study was to investigate seven patients of different ages for beta PP and A beta immunoreactivities associated with PrP-amyloid deposits and degenerating neurites. In one asymptomatic individual with PrP-amyloid deposits, Alz50 and A beta immunoreactivities were absent. In six symptomatic patients, the degenerating neurites surrounding PrP-amyloid deposits were labeled by Alz50 and by antibodies to synaptophysin, ubiquitin and the N- and C-terminal domains of beta PP. In one symptomatic, senile patient, A beta immunoreactivity was present in the extracellular space, often in association with PrP-amyloid deposits. The analysis of the immunohistochemical findings suggested that in the Indiana kindred the intracellular accumulation of beta PP, synaptophysin and ubiquitinated material most probably revealed a reaction of neurites to PrP-amyloid, whereas the extracellular deposition of A beta was likely an age-related phenomenon