Fig. 1

Axonal AT8 phosphorylation in the mossy fiber pathway occurs in the absence of DG cell body pathology. (a) AT8 staining in the dentate gyrus granule cell layer (DG) and their corresponding mossy fiber terminal fields in the stratum lucidum of CA3 (Str. Luc.) across Braak stages. All sections were counter stained with cresyl violet. The increase in cell body staining positively correlates with Braak staging (see Table 2). Scale bars are 25 μm. Quantification of cell body staining using total enumeration indicates the low number of positive cells in these cases. 71.4% of cases (30 of 42) displayed five or fewer cells stained in the DG, with 16.7% (7 of 42) showing no observable cell body pathology (see Table 3). By comparison, 100% of cases displayed axonal AT8 staining in the CA3 Str. Luc. (b). Spearman correlation analysis of AT8+ axonal density and cell body number in the mossy fiber pathway. Data points are plotted as each individual case. A strong, positive correlation (r = 0.640, p ≤ 0.0001) indicates an increase in axonal pathology as cell body pathology increases. (c-d). Representative images from cases with sparse (c) and dense (d) AT8+ mossy fiber axons in cases lacking cell body pathology demonstrate the extent of axonal pathology that can occur prior to observable somatodendritic pathology. Scale bars are 50 μm