The pathological distinctions between the various clinical and pathological manifestations of
frontotemporal lobar degeneration (
FTLD) remain unclear. Using
monoclonal antibodies specific for 3- and 4-repeat
isoforms of the
microtubule associated protein, tau (3R- and 4R-tau), we have performed an immunohistochemical study of the tau pathology present in 14 cases of sporadic forms of
FTLD, 12 cases with Pick bodies and two cases without and in 27 cases of familial
FTLD associated with 12 different mutations in the tau gene (MAPT), five cases with Pick bodies and 22 cases without. In all 12 cases of sporadic
FTLD where Pick bodies were present, these contained only 3R-tau
isoforms. Clinically, ten of these cases had
frontotemporal dementia and two had progressive
apraxia. Only 3R-tau
isoforms were present in Pick bodies in those patients with familial
FTLD associated with L266V, Q336R, E342V, K369I or G389R MAPT mutations. Patients with familial
FTLD associated with exon 10 N279K, N296H or +16 splice site mutations showed tau pathology characterised by neuronal neurofibrillary tangles (NFT) and glial cell tangles that contained only 4R-tau
isoforms, as did the NFT in P301L MAPT mutation. With the R406W mutation, NFT contained both 3R- and 4R-tau
isoforms. We also observed two patients with sporadic
FTLD, but without Pick bodies, in whom the tau pathology comprised only of 4R-tau
isoforms. We have therefore shown by immunohistochemistry that different specific tau
isoform compositions underlie the various kinds of tau pathology present in sporadic and familial
FTLD. The use of such tau
isoform specific
antibodies may refine pathological criteria underpinning
FTLD.