Журнал болезни Альцгеймера и паркинсонизма

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Toll-Like Receptor Signaling in Alzheimer's Disease Progression

Eric J Downer

Evidence continues to underpin the role of the innate immune system in pathologies associated with neuroinflammation. Neuroinflammation is the complex innate immune response of neural tissue to control infection, and Toll-like receptors (TLRs), a major family of pattern recognition receptors (PRRs) that mediate innate immunity, have emerged as players in Alzheimer’s disease (AD). Upon ligation with their ligand, TLRs induce signaling involving recruitment of various adaptors and signaling molecules that culminate in the activation of genes including interferons and cytokines. TLR expression has been identified on resident central nervous system cells including microglia and neurons, with an altered expression profile for this receptor determined in microglia from AD patients. Furthermore, TLR activation on microglia is associated with amyloid-β (Aβ) clearance from the brain, suggesting that modulation of TLR signaling may be a therapeutic strategy for plaque removal. This review will highlight evidence linking the TLR system with the progression of AD, assessing TLR involvement in events associated with AD in cellular systems, transgenic murine models of AD and in humans.