Regulation of the frontocortical sodium pump by Na + in Alzheimer’s disease: difference from the age-matched control but similarity to the rat model

The Na + and K + dependence of the frontocortical Na,K-ATPase in Alzheimer’s disease (AD) was compared with that in human control (Co) and rat AD model. In AD, the relationship between the Na/K ratio and the Na,K-ATPase activity showed noticeable left-shift with three-fold increase in the enzyme affinity for Na + ( K 0.5=10 and 30 mM in AD and Co, respectively). The Na + dependence of the enzyme in AD showed two different Hill coefficients ( n H), 1.1 and 0.3, whereas the Co value of n H was higher (1.4). The rat AD model generated by ibotenic acid revealed a Na + dependence similar to AD. The K + dependence of the Na,K-ATPase showed no significant difference in AD and Co. Compared with Co, AD produced a shift in the break of the Na,K-ATPase Arrhenius plot, suggesting remarkable alterations in the enzyme lipid environment. Our findings support the hypothesis that dysfunction of the Na,K-ATPase in AD is provoked by altered Na + dependence of the enzyme. An impairment of the pump functionality might serve as an early mechanism of AD that should be interrupted by selective pharmacological agents.