From the center of an A-beta deposit, the neuronal density is calculated as a function of the distance from the center. Neuronal densities that correspond to different deposits are superposed, and finally the average neuronal density around a typical deposit is found in dependence on the distance from the center of the deposit.
For each case separately, three graphs are plotted, (a) A-beta deposits are classified into three classes according to their average radia, (b) A-beta deposits are classified into three classes according to their average optical density, and (c) A-beta deposits are classified according to the presence of ThioS, either as fibrils or as dense ThioS+ core in the center of A-beta deposit.
Exceptions are the control cases 444 and 468 that do not have enough deposits to do a reliable calculation. Although the control case 493 has a lot of deposits, they are very different from the rest of the cases: most of them are huge (radius around 100-200 micrometers) and very diffuse (optical density very small compared to the rest of the deposits). The presence of ThioS is mostly sparse, but there is a rather large population of A-beta with ThioS+ core (which makes them look similar to A-beta deposits in PsAPP transgenic mice).
Majority of AD cases (311, 314, 324, and 408) have ThioS uniformly spread over the tissue. The exceptions are the cases 517 and 523, in which ThioS seems to be very sparse. Mostly, it is much more difficult to find the A-beta with ThioS core, because the fibrils are everywhere and even when there is a ThioS core, it is as big as A-beta deposit itself and less optically dense as in control cases.
We can classify the total population of A-beta with respect
to their size, optical density and presence of ThioS roughly
into five classes:
(a) huge diffuse (radius 100-200 micrometers, very low
optical density) A-beta deposits with only sparse
presence of ThioS fibrils, if any;
(b) small diffuse (radius 10-20 micrometers, low optical
density) A-beta deposits with only sparse presence of
ThioS fibrils, if any;
(c) dense A-beta deposits of all sizes with no ThioS present;
(d) dense A-beta deposits of all sizes with ThioS fibrils,
but no ThioS+ core;
(e) dense and predominantly (although not exclusively) large
(radius 30-50 micrometers) with a well defined dense
ThioS core.
Class (a) is found only in the control case 493 and it does
not correlate with any change in the local neuronal density.
Class (b) is found in control as well as AD cases and it
poorly correlates with the local neuronal loss. Class (e) is
found in both control and AD cases and it is always
correlated with a strong decrease in the local neuronal
density. For classes (c) and (d) no general conclusion is
possible so far: Both classes are found in control and AD
cases. In control cases (actually only the case 458) where
class (c) is predominant those two classes are not correlated
with any local neuronal loss. In AD cases, however, class
(d) is the predominant and always correlates with local
neuronal loss, and class (c) which is found only in AD cases
517 and 523 is correlated with local neuronal loss as well (a
little controversial?). Below are more detailed conclusions,
separate for control and AD cases, respectively.
The results from the 2 analyzed control cases suggest:
(1)
large diffuse deposits are not correlated with a decrease in
local neuronal density;
(2) large and optically dense A-beta deposits are correlated
with the decrease in neuronal density;
(3) presence of ThioS fibrils inside A-beta deposits
does not alter the local neuronal density significantly; and
(4) ThioS positive core within A-beta seems to be strongly
correlated with the local decrease in neuronal density.
The conclusions from the 6 analyzed AD cases are:
(1) all the A-beta deposits are correlated with a significant
decrease of the local neuronal density; and
(2) the radius of the neuronal density decrease scales with
the average radius of A-beta deposits---the bigger the
deposit the more extended is the decrease in the neuronal
density.
It is difficult to make conclusions about the influence of
ThioS. The reason may be that ThioS fibrils are uniformly
distributed within the tissue, and the Thios core is not so
well defined either: in many cases the ThioS core
practically coincides with the A-beta deposit and is less
(optically) dense as in control cases. The AD cases 517 and
523 do not look like the rest of AD cases: ThioS is very
sparse and there is almost no A-beta deposits with ThioS+
core. However, larger and optically denser A-beta deposits
are still correlated with the decrease in the local neuronal
density.