Misfolded proteins such as amyloid and tau found in Alzheimer’s disease (AD), β-sheet ligands bind, is one of the therapeutic targets in neurodegenerative diseases. Frontotemporal lobar degeneration (FTLD) is clinically, pathologically, and genetically heterogenous neurodegenerative disease that affects the frontal and temporal lobes of the brain. FTLD with TDP-43 inclusions (FTLD-TDP) is pathologically characterized by the abnormal accumulation of phosphorylated TDP-43 in the cells and can be classified into several types (Types A, B, C, D, and E) based on its morphology and neuroanatomical distribution. Recently, it was reported that some cases of FTLD-TDP-A had high density of thioflavin-S, which is one of β-sheet ligands, positive astrocytosis despite their significance and protein components remain unknown. Our screening process using β-sheet ligands also identified similar findings in FTLD-TDP-A cases. The aim of this study was to chemical-biologically characterize β-sheet ligands positive　astrocytosis and purify proteins composed of β-sheet ligands positive astrocytosis. Initially, we performed fluorescence staining of BF-188, which is one of β-sheet ligands and conformation responsive fluorescence probe. BF-188 stained astrocytosis in FTLD-TDP-A, which emits red fluorescence, it was different from other neuropathogical lesions such as TDP-43, tau, amyloid-β, and α-synuclein in autopsy-confirmed human brain sections. In addition, we found that β-sheet ligands positive astrocytic structure was not merged with phosphorylated TDP-43 immunostaining and ubiquitin immunostaining. To purify proteins composed of β-sheet ligands positive astrocytosis in FTLD-TDP-A, we performed pull-down assays against human brain homogenates using β-sheet ligand immobilized ferrite glycidyl methacrylate beads. We found that around 37kDa bands were selectively observed in FTLD-TDP-A, not control subjects in sodium dodecyl sulfate polyacrylamide gel electrophoresis. Further proteome analysis was ongoing to identify proteins composed of thioflavin-S positive astrocytosis.