ThioS staining versus non-ThioS deposit

Since the proportion of ThioS immunoreactive $A\beta$ deposits increases with $A\beta$ deposit size, we hypothesized that the larger and more dense $A\beta$ deposits were associated with neurotoxicity because they contain fibrillar rather than diffuse $A\beta$. We divided the R1282 immunoreactive deposits as ThiosS positive deposits number of $A\beta$ deposits are in the figure caption (X +/- X) and ThioS negative deposits (X +/- X). For non-ThioS deposits, Fig. 5(a), we observe no significant deviations from the constant line of radial density, suggesting that non-fibrillar $A\beta$ deposits are indeed non-toxic diffuse lesions that do not affect neuronal organization, irrespective of size or staining intensity. Within ThiosS positive deposits there is a remarkable reduction in radial density for all $A\beta$ deposit sizes (Fig. 5(b)). Plaques over $12\mu m$ in radius were associated with a 50% reduction in neuronal density. These data suggest that the toxicity noted with the larger R1282 $A\beta$ deposits is entirely due to ThioS staining deposits.

We next asked if the toxicity of ThioS staining deposits extended beyond the ThioS positive core-whether there was a ``penumbra'' of toxicity. The radial density function $\rho(r)$ was subjected to a linear transformation so that the radial density function for each $A\beta$ deposit was shifted by the radius of the $A\beta$ deposit itself. Thus, in the transformed x-axis, $R=0$ represents the $A\beta$ deposit surface, positive $R$ represents the distance from the $A\beta$ deposit surface, negative $R$ represents the distance from the $A\beta$ deposit surface to an interior region of the $A\beta$ deposit. Figure 6 demonstrates that the neuronal density plummets within the ThioS core, but is normal within $10\mu m$ of its surface, independent of size, suggesting no detectable penumbra effect beyond the ThiosS region. Note: here, $A\beta$ deposit refers to Thios core.