Cortical load of PHF-tau in Alzheimer's disease is correlated to cholinergic dysfunction

To assess a potential relationship between cortical neurofibrillary degener ation and cortical cholinergic deafferentation, the load of PHF-tau was ana lysed in eight cortical regions and in the basal nucleus of Meynert in 12 c ases with Alzheimer's disease by means of a sensitive ELISA employing the m onoclonal antibody B5-2. The activity of choline acetyltransferase was dete rmined on identical tissue samples. The results demonstrate a highly correl ative relationship between the cortical distribution of the amount of PHF-t au, mainly present in neuropil threads, and cholinergic depletion early dur ing the course of the disease. This relationship was less strong in more ad vanced stages. The results support the suggestion that the formation of PHF -tau in cholinergic axon terminals which might result in a loss of choliner gic synapses and a cholinergic dysconnection of the cortex, is an early eve nt in AD. During the progression of the disease, formation of PHF-tau appea rs to spread over the cortex which results in a more even distribution of n europil threads and a progressive involvement of non-cholinergic neurons.