Atypical multiple system atrophy is a new subtype of frontotemporal lobar degeneration: frontotemporal lobar degeneration associated with α-synuclein
Silver staining profiles of Pick bodies (PBs) and their relation to tau-like immunoreactivity were examined on hippocampal sections and compared with those of neurofibrillary tangles of Alzheimer type (NFTs). Pairs of mirror sections were double-fluorolabeled with an anti-paired helical filament tau (AT8) antibody and thiazin red (TR), a fluorochrome that identifies fibrillary structures such as NFTs. One of the paired sections was subsequently stained using the Gallyas method (GAL), and the other using the Campbell-Switzer method (CS). By comparison of the same microscopic field on fluorolabeled sections and on both silver-stained paired sections, four different profiles of each structure could be distinguished: AT8 immunoreactivity, affinity to TR, argyrophilia with GAL or CS staining. PBs, containing mainly three-repeat (3R) tau, were positive for CS but not for GAL and its affinity to TR was, at most, weak. This selective affinity of PBs to CS is in sharp contrast with tau-positive structures of corticobasal degeneration/progressive supranuclear palsy, which are positive for GAL but not for CS, as we reported previously. This contrast is explainable if the argyrophilia with CS is related to deposits containing 3R tau, while that with GAL is linked to those containing four-repeat (4R) tau. Indeed, NFTs, containing both 3R and 4R tau, are positive for both CS and GAL, as expected. Taken together, differences in molecular composition of tau protein in these deposits are linked to their argyrophilic properties that are dependent on the staining method. Although explanations for these empirical differences are not yet available, awareness of this clear distinction is potentially of diagnostic and pathological relevance.