Anti-tau phospho-specific Ser262 antibody recognizes a variety of abnormal hyper-phosphorylated tau deposits in tauopathies including Pick bodies and argyrophilic grains

The rabbit polyclonal anti-tau phospho-specific Ser(262) antibody (577814 Calbiochem) recognizes disease-specific band patterns on Western blots of sarkosyl-insoluble fractions in Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), argyrophilic grain disease (AGD) and Pick's disease (PiD): four bands of 74/72, 68, 64 and 60 kDa in AD, two bands of 68 and 64 kDa in PSP, CBD and AGD, and two bands of 64 and 60 kDa in PiD. Moreover, anti-tau phospho-specific Ser(262) decorates neurons with neurofibrillary tangles, neurons with pre-tangles, dystrophic neurites of senile plaques, neuropil threads, Pick bodies, argyrophilic grains, and coiled bodies. Achromatic neurons in CBD, ballooned neurons in AGD, tufted astrocytes in PSP, astrocytic plaques in CBD and tau-containing astrocytes in AGD are not immunostained with the anti-tau phospho-specific Ser(262) antibody. The lack of phospho-specific Ser(262) immunoreactivity in tau-containing inclusions in astrocytes suggests different kinase equipment and activation in comparing neurons and astrocytes in tauopathies. Pick bodies in PiD and grains in AGD are weakly, or not all, immunostained in tissue samples with long postmortem delays, although Ser(262) is preserved in brain homogenates corresponding to the same time points processed for Western blot. This indicates postmortem modifications of tau in Pick bodies and argyrophilic grains, but not in other tau-containing inclusions, including paired helical filaments and coiled bodies, and suggests differences in tau conformation, particularly that involving phospho-tauSer(262) among tauopathies. However, it is important to note that phosphorylation of tau at Ser(262) does occur in Pick bodies and argyrophilic grains, and this may have important consequences in reducing the capacity of binding phospho-tau to microtubules in these inclusions.