NERVE GROWTH-FACTOR REVERSES NEURONAL ATROPHY IN A DOWN-SYNDROME MODEL OF AGE-RELATED NEURODEGENERATION

Atrophy and dysfunction of certain neurons, including cholinergic neur ons in the basal forebrain, are key features of the neuropathology of Alzheimer's disease (AD). Since all individuals with Down syndrome (DS ) develop AD neuropathology by the 4th decade, we reasoned that a gene tic model of DS, the trisomy 16 (Ts 16) mouse, may provide an animal m odel to study the neurodegeneration in AD. Ts 16 mice fail to survive birth; to evaluate neurons for long periods in vivo required transplan tation of fetal tissue. We previously demonstrated that Ts 16 basal fo rebrain cholinergic neurons (BFCNs) undergo age-related atrophy simila r to DS and AD, and now show that a specific neurotrophic factor, nerv e growth factor (NGF), acts to reverse Ts 16-induced atrophy of BFCNs and stimulates hypertrophy of these cells. As NGF levels were not decr eased in the host, abnormalities intrinsic to Ts 16 BFCNs presumably c aused the atrophy. Our results suggest that NGF may be useful in rever sing cholinergic neurodegeneration in DS and AD.