Astrocyte Senescence and Alzheimer’s Disease: A Review
Han X, Zhang T, Liu H, Mi Y, Gou X. Astrocyte Senescence and Alzheimer’s Disease: A Review. Front Aging Neurosci. 2020 Jun 9;12:148. doi: 10.3389/fnagi.2020.00148. PMID: 32581763; PMCID: PMC7297132.
This review examines findings about astrocyte senescence and its relationship with AD as well as the potential therapeutic value this research. Astrocytes “perform critical roles in regulation of homeostasis and metabolism of the neurons, mediating uptake and recycling of neurotransmitters. Astrocytes also play a key role in maintenance of the blood–brain barrier (BBB). They also act as modulators of synaptic plasticity and transmission, supporting the view that astrocytes play an integral role in the initiation and progression of cognitive decline and AD.”
Astrocytes undergo stress-induced premature senescence and Aβ oligomers can induce senescence and promote the production of SASP in human astrocytes. Bhat et al showed that after exposure to Aβ1-42 astrocytes show senescence characteristics, particularly those from AD brains. Senolytic or genetic ablation of senescent astrocytes and microglia prevents NFT formation and neurodegeneration in mice.
Aβ clearance
Astrocytes play an important role in clearing and degrading Aβ and the receptors involved (low-density lipoprotein receptor-related protein 1 (LRP1) and scavenger receptor B1 (SR-B1)) reduce in expression in aged astrocytes. The appearance of senescent astrocytes was “earlier than Aβ accumulation. The proinflammatory factors senescent astrocytes secrete can increase APP expression and Aβ generation in neurons.
NFT
Neurons carrying NFTs become senescent and cause toxicity to nearby neurons. NFT containing neurons has increased cellular senescence hallmarks and upregulation of senescence associated genes. Clearing senescent astrocytes prevented NFT deposition and hyperphosphorylated tau.
Synaptics
“astrocytes play a critical role in supporting neuronal growth and modulating synaptic function and transmission, yet the neuroprotective capacity of astrocytes decreased during aging”.
Inflammation
Senescent astrocytes may promote inflammation in AD brains and contribute to pathogenesis.