Fig. 7

Correlative autoradiography (ARG) and immunohistochemical (IHC) findings for assessment of TDP-43 binding in cases with different phenotypic TDP-43-like presentations. a-c Case 29 – AD pathologically, d-f Case 30 - FTLD-TDP, g-i Case 31 - FTLD-TDP, j-l Case 32 - FTLD-TDP. Shown from left to right AV-1451 ARG (AV-1451 blocking shown in the ARG insets), and PHF-1 in the a-i amygdala and j-l frontal cortex. a-c A TDP-43-negative AD case presenting clinically as semantic variant of primary progressive aphasia (svPPA) shows strong ARG displaceable binding in insula (green arrow), claustrum (green arrowhead), and NBM (black arrowhead with inset, tangles) and amygdala (black arrow with IHC inset, tangles) with correspondence on PHF-1 IHC. d-f The amygdala region in a FTLD-TDP case presenting as an agrammatic variant of PPA (agPPA) with TDP-43 type A at autopsy, shows a negative PHF-1 and minimal diffuse ARG binding with a weak correspondence (red arrows) with TDP-43 pathology (TDP-43 inset, cytoplasmic and intranuclear inclusions). Strong off-target binding of the vasculature (blue arrow) appears to correspond with mineralization of the vessel and potentially with subpial melanin lentiform-shaped inclusion (upper inset). g, i Similarly, the amygdala of the FTLD-TDP case presenting as FTD with TDP-43 type A at autopsy was negative on PHF-1 and minimally positive on TDP-43. The ARG displaceable binding shows a weak correspondence (red arrows) with TDP-43 pathology (inset). Strong off-target binding of the vasculature (blue arrow) appears to correspond with cross-reactivity to red blood cells (H upper inset). j-l Frontal cortex in a FTLD-TDP case presenting clinically as semantic variant PPA (svPPA) with TDP-43 Type-C at autopsy was negative on PHF-1 and positive on TDP-43. ARG shows minimal displaceable binding in cortex that corresponds (red arrows) to TDP-43 pathology (inset, long thick dystrophic neurite). Scale bar for all full size brain sections at 5 mm, and for 20x zoomed insets at 25 μm. Black arrowheads indicate 20x inset locations