Fig. 4

Multiple Alzheimer’s disease etiologies and many cellular partners. Deleterious proteinopathies (in the first-place amyloid peptides) are to be integrated into the complex cellular environment of the brain. These multiple cellular elements participate in progressive multi-focal neuro-axonal degeneration leading to the irreversible symptomatology of AD. This is expressed when the toxic peptide removal systems are overwhelmed, which appears only after a long incubation period. Altered neurons express phases of hypo- and hyperexcitability with deficits in axonal transport and synaptic activity that affects myelination/remyelination activity and oligodendrocyte trophism. These are very vulnerable cells whose density decreases sharply with age. There seems to be a link between the intensity of neuronal involvement and the extent of demyelination. This is strongly accentuated in AD in which remyelination processes seem deficient. The activation of astrocytes participates in the elimination of deficient neurons and synapses. They actively participate in the elimination of abnormal proteins and inflammation processes, in the same way that the activation of microglia facilitates the phagocytosis of cellular debris. In the same way, these cells participate in the activation of the innate immune responses, the activation of the complement and the secretion of inflammatory cytokines. Abbreviations: AD, Alzheimer’s disease; ROS, reactive oxygen species