Fig. 5

Specificity of glial responses to Lin bodies in neurodegenerative conditions. This figure compares the response of GFAP (A-C), IBA1 (D-F), and ferritin (G-H) in proximity to Lin body-positive vessels and pTDP-43-negative vessels of similar diameter, as shown in panel A. Panels A, D, and G illustrate automated tissue analysis markups for the Object Colocalization algorithm and the Area Fraction algorithm, showing what the software counted as cells and staining burden, respectively. The cell counts for GFAP, IBA1, and ferritin identified by this algorithm are displayed in panels B, E, and H, respectively. Within-case comparisons are made between LATE-NC Lin body-positive vessels (marked with yellow circles) and pTDP-43 negative vessels in the same LATE-NC cases (indicated by red squares). These are compared to pTDP-43 negative vessels in AD-NC cases (represented by blue triangles). Panels C, F, and I show the positively stained areas, as determined by the Area Fraction algorithm. Lin body-positive cases (indicated by yellow circles) exhibited a greater staining area than pTDP-43 negative vessels (red squares) within the same case for GFAP, IBA1, and ferritin (C, F, I). Vessels from pTDP-43 negative ADNC cases (blue triangles) showed the lowest levels of GFAP, IBA1, and ferritin in both cellular profiles (B, E, H) and staining area (C, F, I), compared to LATE-NC cases, regardless of ADNC pathology (AD +/-). Circles, squares, and triangles represent individual case results, with bars indicating the mean +/- SEM. Detailed statistical comparisons are provided in Table 2