Alzheimer’s disease β- Amyloid protein tangles with Tau neurofibrils. Several enzymes (e.g β- Secretase and γ- Secretase) on transmembrane proteins β- Cutting production of amyloid precursor protein (APP) β- Amyloid peptide (about 40 amino acids). β- The extracellular accumulation of amyloid peptide leads to senile plaque deposition, which is related to pathological Tau and neuronal cell death. Tau is a microtubule associated protein that participates in the assembly of stable microtubule proteins. In Alzheimer’s disease, hyperphosphorylated Tau protein accumulates and forms neurofibrillary tangles in neurons. Reprinted from BioRender Com (2021).
However, the results of Alzheimer disease animal models and human studies show that, β- Amyloid protein deposition may not cause neurotoxicity. On the contrary, there is more and more evidence indicating the role of other APP derivatives, such as the carboxyl terminal fragment of APP. In addition, Tau inclusion is associated with Alzheimer’s disease β- Amyloid deposition is not relevant (Kametani and Hasegawa 2018).
Finally, the involvement of neuroinflammatory processes in Alzheimer’s disease, including the release of substances (such as cytokines) and the activation of astrocytes and microglia, has recently become an important pathogenesis (Fackhoury 2018). Although astrocytes and microglia have been proved to be involved β- The removal of amyloid, but their activity may also be proinflammatory. Therefore, the role of glial cells in the pathogenesis of Alzheimer’s disease is unclear, because they can both promote and prevent neurotoxicity.
Astrocyte microglial communication in alzheimer’s disease
Recent work by McAlpine of Harvard Medical School and his colleagues highlights the IL3-IL3 receptor α The correlation between (CD123) signal transduction and the communication between astrocytes and microglia in Alzheimer’s disease. McCall is equal. It is proved that in the case of Alzheimer’s disease (i.e., 5xFAD mice), the expression of IL3 is critical for the elimination of β- Amyloid protein and prevention of cognitive decline are essential. The team clarified that brain derived rather than systemic expression of IL3 is crucial for the protection of Alzheimer’s disease, and continued to trace the origin of IL3 to a subset of astrocytes. Although the expression of IL3 by astrocytes is constitutive and not affected by the background (i.e. WT and 5xFAD), the expression of IL3 receptor is specifically induced in microglia of Alzheimer’s brain. It is worth noting that McAlpine and his colleagues found that the induction of IL3 receptor depends on the expression of TREM2 (trigger receptor 2 expressed on myeloid cells), which is a previously determined degradation of microglia β- A crucial receptor for amyloid (Zhao et al., 2018).
The in-depth study of various molecular markers enables researchers to identify TREM2 positive microglia subsets with high IL-3 receptor expression and activation phenotype. In addition, tampering with the expression of IL3 receptors in 5xFAD mice can disrupt the molecular processes that control the morphology and movement of microglia. In fact, on the whole, the team found that IL3 signal transduction formulated to promote microglia navigation and aggregation β- Molecular programs surrounding amyloid aggregates. Astrocyte derived IL3 is critical for microglial activation, and its deletion increases β- Amyloid protein deposits and reduces microglia’s β- Localization of amyloid aggregates.
Researchers found evidence of activated microglia that can induce the expression of IL3 receptor in postmortem cortical brain samples of patients with Alzheimer’s disease, and researchers are confident about the correlation of this pathway in disease pathology. Finally, McAlpine and colleagues showed that direct administration of IL3 to the 5xFAD brain resulted in microglia activation and aggregation β- Amyloid aggregates surround and are associated with improved memory. In conclusion, their findings provide impetus for therapeutic strategies that target astrocyte microglial communication by regulating IL3 signaling.