Silver stains distinguish tau-positive structures in corticobasal degeneration/progressive supranuclear palsy and in Alzheimer's disease--comparison between Gallyas and Campbell-Switzer methods.
ABSTRACT Possible differences in silver-staining profiles and their relation to tau-like immunoreactivity were investigated on cortical sections from corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), Down's syndrome (DS) and Alzheimer's disease (AD). Pairs of mirror sections were double-fluorolabeled with an anti-PHF tau (AT8) antibody and thiazin red (TR), a fluorochrome that labels fibrillary structures such as neurofibrillary tangles (NFTs). Subsequently, one of the pair was stained with Gallyas method (GAL), and the other with Campbell-Switzer method (CS). Identification of the same structure on the corresponding microscopic fields enabled a comparison of four different profiles of each structure: AT8 immunoreactivity, and affinity to TR, GAL and CS. NFTs of DS/AD, containing three- and four-repeat tau, were positive for TR, GAL and CS. AT8-immunoreactive structures of CBD/PSP, containing mainly four-repeat tau, were positive for GAL, but negative for CS and TR. This discrepancy is explainable if the argyrophilia with GAL is related to deposits containing four-repeat tau, while that with CS is linked to those containing three-repeat tau. The lack of CS labeling may also be related to poor TR staining, possibly representing scarcity of fibrillary structure in CBD/PSP. The absence of CS staining is characteristic of tau-positive structures of CBD/PSP, which is readily distinguishable from NFTs of DS/AD, hence is of potential pathological and diagnostic relevance.
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ABSTRACT: Frontotemporal lobar degeneration (FTLD) is the umbrella term encompassing a heterogeneous group of pathological disorders. With recent discoveries, the FTLDs have been show to classify nicely into three main groups based on the major protein deposited in the brain: FTLD-tau, FTLD-TDP and FTLD-FUS. These pathological groups, and their specific pathologies, underlie a number of well-defined clinical syndromes, including three frontotemporal dementia (FTD) variants [behavioral variant frontotemporal dementia (bvFTD), progressive non-fluent aphasia, and semantic dementia (SD)], progressive supranuclear palsy syndrome (PSPS) and corticobasal syndrome (CBS). Understanding the neuropathological background of the phenotypic variability in FTD, PSPS and CBS requires large clinicopathological studies. We review current knowledge on the relationship between the FTLD pathologies and clinical syndromes, and pool data from a number of large clinicopathological studies that collectively provide data on 544 cases. Strong relationships were identified as follows: FTD with motor neuron disease and FTLD-TDP; SD and FTLD-TDP; PSPS and FTLD-tau; and CBS and FTLD-tau. However, the relationship between some of these clinical diagnoses and specific pathologies is not so clear cut. In addition, the clinical diagnosis of bvFTD does not have a strong relationship to any FTLD subtype or specific pathology and therefore remains a diagnostic challenge. Some evidence suggests improved clinicopathological association of bvFTD by further refining clinical characteristics. Unlike FTLD-tau and FTLD-TDP, FTLD-FUS has been less well characterized, with only 69 cases reported. However, there appears to be some associations between clinical phenotypes and FTLD-FUS pathologies. Clinical diagnosis is therefore promising in predicting molecular pathology.Acta Neuropathologica 05/2011; 122(2):137-53. · 9.32 Impact Factor
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ABSTRACT: Silver-staining methods are helpful for histological identification of pathological deposits. In spite of some ambiguities regarding their mechanism and interpretation, they are widely used for histopathological diagnosis. In this review, four major silver-staining methods, modified Bielschowsky, Bodian, Gallyas (GAL) and Campbell-Switzer (CS) methods, are outlined with respect to their principles, basic protocols and interpretations, thereby providing neuropathologists, technicians and neuroscientists with a common basis for comparing findings and identifying the issues that still need to be clarified. Some consider "argyrophilia" to be a homogeneous phenomenon irrespective of the lesion and the method. Thus, they seek to explain the differences among the methods by pointing to their different sensitivities in detecting lesions (quantitative difference). Comparative studies, however, have demonstrated that argyrophilia is heterogeneous and dependent not only on the method but also on the lesion (qualitative difference). Each staining method has its own lesion-dependent specificity and, within this specificity, its own sensitivity. This "method- and lesion-dependent" nature of argyrophilia enables operational sorting of disease-specific lesions based on their silver-staining profiles, which may potentially represent some disease-specific aspects. Furthermore, comparisons between immunohistochemical and biochemical data have revealed an empirical correlation between GAL+/CS-deposits and 4-repeat (4R) tau (corticobasal degeneration, progressive supranuclear palsy and argyrophilic grains) and its complementary reversal between GAL-/CS+deposits and 3-repeat (3R) tau (Pick bodies). Deposits containing both 3R and 4R tau (neurofibrillary tangles of Alzheimer type) are GAL+/CS+. Although no molecular explanations, other than these empiric correlations, are currently available, these distinctive features, especially when combined with immunohistochemistry, are useful because silver-staining methods and immunoreactions are complementary to each other.Acta Neuropathologica 05/2007; 113(5):483-99. · 9.32 Impact Factor