Interaction of rat brain phosphofructokinase with Alzheimer's beta A4-amyloid

One of the key functional disturbances in incipient dementia of Alzheimer type is the reduction of cerebral glucose utilization. Morphologically the brains of Alzheimer patients are characterized by multiple depositions of beta A4-amyloid mainly within extracellular senile plaques and in the walls of cerebral blood vessels, but also attached to intracellular neurofibrillary tangles. Intracellular beta A4-amyloid may bind to other cellular components. The interaction of beta A4-amyloid with phosphofructokinase, one of the key enzymes in glycolysis, was studied in vitro under various conditions. beta A4-amyloid was found to bind in nanomolar concentrations to phosphofructokinase and decrease its activity. Binding was demonstrated by enzyme linked immunoassays and by gel filtration studies. Inactivation of phosphofructokinase by beta A4-amyloid could only partially be prevented by fructose 6-phosphate. In control experiments no interaction was detectable between lactate dehydrogenase and beta A4-amyloid.