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PublicationWhite Matter Evaluation Techniques in Frontotemporal Dementia(2022-05-01) Kopp, EmilyFrontotemporal dementia (FTD) is a category of early-onset, progressive dementias that present with behavioral or language impairments. FTD is typically caused by one of two proteinopathies: either tau or TDP-43. Limited information is known about how the pathologies differentially impact white matter (WM) degeneration in FTD. With a cohort of human anterior cingulate brain tissue samples from healthy controls and FTD patients, this study used immunohistological staining to assess WM evaluation techniques and study differences between the FTD-tau and FTD-TDP pathologies. In a small cohort of 30 cases, serial sections of tissue were stained with LFB, MBP, SMI-35, and a cresyl violet control. The tissue was then analyzed with structure tensor imaging software to identify differences in fiber anisotropy and digital stain quantification tools. Limitations for structure tensor imaging software were identified, as were best stains for future analysis. No statistically significant differences between the FTD-tau, FTD-TDP, and healthy cases were observed in this group. In an expanded cohort of 181 cases, anterior cingulate tissue stained with SMI-35 was evaluated. Analysis revealed significantly less SMI-35 staining for FTD-tau cases against healthy controls (p-value = 0.002202 for the %AO measure) and FTD-TDP cases against healthy controls (p-value = 0.01077 for the %AO measure). There was no difference observed between the FTD-tau and FTD-TDP cases. These early findings show evidence that both proteinopathies of FTD experience axon degeneration in the anterior cingulate compared to healthy controls. These results also support future use of the SMI-35 antibody and digital stain quantification methods.