Alzheimer's disease (AD) is the most common cause of dementia in the elderly and there is currently no effective treatment. AD places a tremendous physical, emotional and economic burden on its sufferers, their families and society. While the pathogenesis of AD is not fully understood, the prominent neuropathological features in AD are brain amyloid deposition, neurofibrillary tangles and loss of cholinergic neurons in the basal forebrain. However, the relationship between these features have remained obscure. The correlation of dementia with amyloid plaques and neurofibrillary tangles is not consistent. Instead, the cortical and hippocampal cholinergic dysfunction resulting from the loss of cholinergic neurons in the basal forebrain is documented to contribute to cognitive deficits, but improvement in cognition by restoration of cholinergic activity has not been satisfactorily achieved. Possibly, none of these features is solely attributed to the most destructive symptom; the dementia. Nonetheless, there may be some connections between these central pathological features in the AD process, and elucidation of such relationships is critical to understanding the progression of AD. We are investigating reciprocal control mechanisms between amyloid precursor protein (APP) related systems, cholinergic activity, neurotrophic factors and their role in cognition.