The relationship between Alzheimer's disease (AD) and progressive degeneration of the forebrain cholinergic system is very well established, whereas mechanisms linking this disease with cholesterol, apolipoprotein E (apoE) phenotype, and amyloid precursor protein (APP) metabolism have not been fully elucidated even though there is a plethora of publications separately on each of these issues. The gene discussed is APP; the disease is early-onset autosomal dominant Alzheimer disease.