Fig. 9

Correlative autoradiography (ARG) and immunohistochemical (IHC) examples of off-target AV-1451 binding. a, b Case 1 - Normal, c, d Case 3 - Normal, e, f Case 19 - PSP, g, h Case 6 - AD (HpSp), i, j Case 36 - MSA, k, l Case 30 - FTLD-TDP, m-p Case 2 - Normal, q-t Case 31 - FTLD-TDP. We present evidence for two major causes of off-target binding (blue arrows), a-j pigment-laden structures and k-t mineralization. Shown from left to right AV-1451 ARG and PHF-1 IHC (except where noted) are shown in the a, b midbrain, c, d, k-p posterior hippocampus, e, f superior temporal, g, h, q-t amygdala, and i, j pituitary. a, b AV-1451 signal is seen in the substantia nigra in all cases in the study (blue arrow); c, d lateral geniculate displaceable (c, inset) in most cases likely owing to the abundance of pigment-containing lipofuscin-filled neurons (inset); e, f vascular structures on some cases in vessels with cross-reactive red blood cells (top inset); g, h subpial coverings in some cases with strong displaceable (g, inset) binding observed in proximity to melanin-containing structures that were also found on non-antibody based stains (h, Prussian blue, inset); i, j moderate AV-1451 binding in the pituitary section is also found to correspond to subpial melanin. k, l Strong, focal AV-1451 binding was observed in the choroid plexus and found to correspond to mineralization of the vessel (inset). m, n ARG of choroid plexus revealed variable binding with some cases showing little-to-no binding. PHF-1 staining did not reveal tau-positive structures in choroid. Closer inspection of choroid with (o) thioflavin-S fluorescent microscopy revealed abundant Biondi in older brains, which corresponded to (p) pigment-containing structures on zoomed PHF-1 slides. s, t Variable involvement of basal ganglia was noted, but was not found to correspond with tau pathology. s A digitally-modified Prussian blue (iron stain) revealed a similar pattern underlying moderate-strong ARG binding. Curiously, pencil fibers were often noted to be Prussian blue positive. Scale bar for all full size and zoomed brain sections are noted within each image. Black arrowheads indicate 20x inset locations