Pharmacological Actions of Recombinant Human Nerve Growth Factor on Lesioned Central Cholinergic Neurons: Rationale for the Treatment of Alzheimer’s Disease

Alzheimer’s disease (AD) is characterized by an extensive degeneration of the cholinergic system of the human septo-hippocampal pathway (Collerton, 1986) which is correlated with severe deficits of cognitive functions (Perry et al., 1978). It has been well established that in AD there are decreases of cholinergic function and cholinergic markers associated with this pathway. These deficits include the loss of cholinergic cell bodies in the basal forebain (Whitehouse et al., 1982; Arendt et al., 1983) and decreased choline acetyltransferase (ChAT) activity in the basal forebrain and hippocampal formation (Perry et al., 1978; Araujo et al., 1988). In addition, the ability of hippocampal cholinergic neurons to synthesize acetylcholine (ACh) is decreased (Sims et al., 1980) possibly due to a reduction in the uptake of choline via the high affinity choline uptake system (Rylett et al., 1983).