Fig. 4.

Axonal PAD exposure in the Schaffer collateral pathway occurs in the absence of CA3 cell body pathology. (a) TNT2 staining in the pyramidal cell layer of CA3 pyramidal cell layer and their corresponding mossy fiber terminal fields in the CA1 stratum radiatum (Str. Rad.) across Braak stages. All sections were counter stained with cresyl violet. The increase in neuropil thread staining positively correlates with Braak staging (see Table 6). Scale bars are 25 μm. Quantification of cell body staining using total enumeration indicates the low number of positive cells in these cases. 71.8% of cases (28 of 39) displayed five or fewer cells stained in the CA3 pyramidal cell layer, with 25.6% (10 of 39) showing no observable cell body pathology (see Table 6). A subset of cases without cell body staining still contained axonal TNT2 staining (see Table 6). (b). Spearman correlation analysis of TNT2+ axonal density and cell body number in the mossy fiber pathway. A moderate, positive correlation (r = 0.423, p = 0.0073) indicates an increase in axonal pathology as cell body pathology increases. (c-d). Representative images from cases with sparse (c) and dense (d) TNT2+ Schaffer collateral 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