The loss of acetylcholine is one of the earliest and most significant losses associated with Alzheimer's disease. We have previously modeled this loss in terms of beta-amyloid- induced leakage of choline out of cholinergic neurons. Because of recent experimental results, we now broaden that treatment to allow for a compensatory increase in high-affinity choline uptake (HACU) and for inhibition of HACU by beta-amyloid. In this model, beta-amyloid limits the availability of acetylcholine both by increasing choline leakage and by inhibiting choline uptake. Thus, an increase in HACU cannot completely compensate for choline leakage.