Figure 1.

(A) Late-onset AD (LOAD) neuropathology affects increasingly wider cerebral cortical areas. LOAD is a spreading disease which starts from the layer II neurons of the lateral entorhinal allocortex (LEC) of the temporal lobe and expands progressively to cognition-related upper neocortical areas. Involved brain tissues undergo deep changes due to concurrent neurotoxic, inflammatory, oxidative, and hypoxic-ischemic processes driven by accumulating Aβ₄₂-os and Aβ fibrils and later by p-Tau-os and causing the death of susceptible neurons. The diagram represents a view of the LOAD-affected areas (in dark blue color) from the medial-inferior hemispheric face at an early (Pre-AD), presymptomatic AD) and a late fully symptomatic stage of the illness. (B) The basic organization of the brain's neurovascular unit (NVU). NVUs are made up by cerebral astrocyte-neurons teams (ANTs) placed in close contact with capillary vessels. In this cartoon, a “master” astrocyte (in green color) emits numerous cytoplasmic processes (of which only a few are depicted here), the end-feet of which enshroud two neuronal synapses, touch the dendrite of a “client” neuron (in blue color), and cover a portion of the outer surface of a capillary vessel (in red color). The neuronal axons are endowed with myelin sheaths (in yellow color). Both neurons and the astrocyte express the CaSR (yellow ovals). By its placement, the astrocyte acts as a bridge between the capillary vessel and the neurons, provides the latter with nutrients brought up by the former, protects synapses, and partakes in the upkeep of the brain-blood barrier (BBB; not shown) functional integrity.