CELLULAR DELIVERY OF NGF DOES NOT ALTER THE EXPRESSION OF BETA-AMYLOID IMMUNOREACTIVITY IN YOUNG OR AGED NONHUMAN-PRIMATES

The present study determined whether grafts of nerve growth factor-pro ducing fibroblasts alter the expression of beta-amyloid in young or ag ed nonhuman primates. Aged monkeys serve as an animal model which norm ally exhibits beta-amyloid-laden plaques. Three young adult (7-12 year s of age) and three aged (24-29 years of age) rhesus monkeys received intraventricular implants of polymer-encapsulated cells that were gene tically modified to secrete human recombinant nerve growth factor (NGF ). Three young adult and three aged rhesus monkeys received identical treatment except that the grafted cells were not genetically modified and thus differed only by a single gene construct. Five additional age d rhesus monkeys were ungrafted and also served as controls. Three to four weeks posttransplantation, young monkeys did not display beta-amy loid-immunoreactive profiles within any CNS structure regardless of tr eatment. Qualitative observations revealed that aged monkeys displayed numerous beta-amyloid plaque-like structures within the amygdala and hippocampus as well as limbic and neocortices. The amount of beta-amyl oid immunoreactivity (beta-amyloid load) was quantified bilaterally wi thin the temporal neocortex of these animals. The beta-amyloid load wi thin the temporal neocortex of aged monkeys was highly variable but di d not differ across treatment groups. These data indicate that chronic short-term administration of NGF does not affect the expression of be ta-amyloid in the young or the aged primate brain. (C) 1997 Academic P ress.