Astrocytes as Neuroimmunocytes in Alzheimer's Disease: A Biochemical Tool in the Neuron-Glia Crosstalk along the Pathogenetic Pathways.

This work aimed at assessing Alzheimer's disease (AD) pathogenesis through the investigation of the astrocytic role to transduce the load of amyloid-beta (Aβ) into neuronal death. The backbone of this review is focused on the deepening of the molecular pathways eliciting the activation of astrocytes crucial phenomena in the understanding of AD as an autoimmune pathology. The complex relations among astrocytes, Aβ and tau, together with the role played by the tripartite synapsis are discussed. A review of studies published from 1979 to 2023 on Scopus, PubMed and Google Scholar databases was conducted. The selected papers focused not only on the morphological and metabolic characteristics of astrocytes, but also on the latest notions about their multifunctional involvement in AD pathogenesis. Astrocytes participate in crucial pathways, including pruning and sprouting, by which the AD neurodegeneration evolves from an aggregopathy to neuroinflammation, loss of synapses and neuronal death. A1 astrocytes stimulate the production of pro-inflammatory molecules which have been correlated with the progression of AD cognitive impairment. Further research is needed to "hold back" the A1 polarization and, thus, to slow the worsening of the disease. AD clinical expression is the result of dysfunctional neuronal interactions, but this is only the end of a process involving a plurality of protagonists. One of these is the astrocyte, whose importance this work intends to put under the spotlight in the AD scenario, reflecting the multifaceted nature of this disease in the functional versatility of this glial population.