Pick bodies and ballooned cells of Pick's disease and the neurofibrillary 
lesions of Alzheimer's disease are characterized by the presence of 
hyperphosphorylated microtubule-associated protein tau. Little is known about 
the mechanisms underlying tau hyperphosphorylation in Pick's disease and the 
distribution of abnormal tau in affected neurons. We have used a panel of 
phosphorylation-dependent (AT270, AT8, AT180, 12E8, PHF-1, AT10 and Tau-1) and 
phosphorylation-independent anti-tau antibodies (N-tau 5 and 134) to stain brain 
tissue sections from subjects with Pick's disease and Alzheimer's disease. These 
antibodies labeled Pick bodies and neurofibrillary lesions in a similar way, 
with the exception of antibody 12E8, which stained a subset of neurofibrillary 
tangles, but no Pick bodies. Moreover, abundant AT8- and PHF-1-positive neuritic 
profiles were observed in cortical areas rich in Pick bodies, even in the 
complete absence of neurofibrillary lesions. Unlike the Gallyas-positive 
neuropil threads of Alzheimer's disease, which were of variable diameter and 
covered by spiny appendages, neuritic profiles of Pick's disease showed a 
regular diameter, appeared smooth and were Gallyas-negative. In contrast to 
Alzheimer's disease, dendritic branches of neurons containing Pick bodies were 
not labeled by anti-tau antibodies. In the hippocampus, numerous tau-positive 
axon terminals were found along dendrites of the polymorphic layer of the 
dentate gyrus. Our results indicate that tau proteins in Pick's disease and 
Alzheimer's disease share similar phosphorylated residues, with the exception of 
serine 262, which is phosphorylated in Alzheimer tangles but not in Pick bodies 
or neuritic profiles. Furthermore, we show that hyperphosphorylated tau 
segregates to different neuronal compartments in the two diseases, with a 
somatoaxonal distribution in Pick's disease and a somatodendritic distribution 
in Alzheimer's disease.