Figure 3.

Propagation of LOAD neuropathology to neighboring astrocyte-neurons teams (ANTs). The cartoon shows that an excess of exogenous Aβ₄₂-os (here short-termed as Aβ₄₂) supposedly reaches first the team of neurons and astrocytes (ANT) at the center and binds their CaSRs (not detailed) triggering signals that end up increasing the secretion of newly produced endogenous Aβ₄₂-os (red and green circles) from all of the ANT's cellular members (# 1–5). Blue arrows indicate the diffusion of Aβ₄₂-os from neurons to astrocytes (red solid circles) and from astrocytes to neurons (green solid circles). Numbers 1–5 also suggest possible sequences of events both intra- and inter-ANTs. While the involved cells undergo cytotoxic changes, including the early death of some neurons (in green color with skull and crossbones aside), the newly released Aβ₄₂-os spread and reach both neighboring and remoter ANTs (short and long red arrows), starting via Aβ₄₂-os•CaSR signaling new cycles of surplus production and secretion of endogenous Aβ₄₂-os. The latter will disperse and engage nearby and still farther away ANTs (not shown) again triggering the same kind of Aβ₄₂-os•CaSR signaling-triggered pathological responses, including additional Aβ₄₂-os oversecretion and neuronal deaths. Thus, Aβ₄₂-os spread can affect local ANTs (as embodied here by the short and long red arrows) or remoter ANTs via projecting axons carrying the Aβ₄₂-os (as exemplified here by the big black arrows).