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.
NIH ExPorter
NIH ExPorter