Innate Immune Cell Death in Neuroinflammation and Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disorder molecularly characterized by the formation of amyloid beta (A beta) plaques and type 2 microtubule-associated protein (Tau) abnormalities. Multiple studies have shown that many of the brain's immunological cells, specifically microglia and astrocytes, are involved in AD pathogenesis. Cells of the innate immune system play an essential role in eliminating pathogens but also regulate brain homeostasis and AD. When activated, innate immune cells can cause programmed cell death through multiple pathways, including pyroptosis, apoptosis, necroptosis, and PANoptosis. The cell death often results in the release of proinflammatory cytokines that propagate the innate immune response and can eliminate A beta plaques and aggregated Tau proteins. However, chronic neuroinflammation, which can result from cell death, has been linked to neurodegenerative diseases and can worsen AD. Therefore, the innate immune response must be tightly balanced to appropriately clear these AD-related structural abnormalities without inducing chronic neuroinflammation. In this review, we discuss neuroinflammation, innate immune responses, inflammatory cell death pathways, and cytokine secretion as they relate to AD. Therapeutic strategies targeting these innate immune cell death mechanisms will be critical to consider for future preventive or palliative treatments for AD.

Automated summary

Alzheimer's disease is a neurodegenerative disorder characterized by the formation of plaques and abnormalities in certain proteins. Immune cells play a crucial role in the development of the disease, as they can cause cell death and release proinflammatory cytokines. However, chronic inflammation can worsen the condition. Therefore, balancing the immune response is important for effectively clearing the abnormal proteins without inducing inflammation.