The Importance of Microglia and Mast Cells in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease of the central nervous system (CNS), results in dementia, memory and cognitive impairment. Main pathological characteristics of AD are extracellular deposits (senile plaques) of fibrillar amyloid b-peptide (Aβ) and intracellular neurofibrillary tangles hyperphosphorylated tau protein, alongside signs of activated Microglia and Astrocytes which isoften related to Aβ deposition. Neuroinflammation is the immune reactions jeopardize CNS components. AD is considered as a neuroinflammatory disease involving immune components of CNS. Microglia plays a macrophage-like role in the CNS immune defense.Microglia are associated with the production and release of pro-inflammatory cytokines, most importantly tumor necrosis factor (TNF)-α, IL-6, IL-23, IL-1β, IL-12, nitric oxide (NO), and chemokines. TLR4 (Toll-like receptor 4) is one of many receptors Microglia uses to detect Aβdeposition. Activated Microglia secretes neurotrophic factors and diminishes the Aβ deposits to protect neurons. Although primary activation of Microglia is beneficial, chronic exposure of TLR4 to Aβ can result in TLR signaling dysfunction and inflammation. Mast cells (MCs) are innate immune system cells, present adjacent to blood vessels of most tissues including CNS. MCs are capable of producing a vast range of mediators including cytokines ((TNF-α), IL-1, 2,3,5,6,7,9,13,16 and 33) chemokines, growth factors and etc. MCs are a key component of allergic and inflammatory reactions by rapid degranulation and then slow release of newly synthesized pro-inflammatory mediators andcytokines. MCs have a close connection with Microglia in inflammatory sites of CNS and they are also capable of detecting Aβ deposition and responding to them through inflammatory mediators. Conclusion: Despite MCs close attachment to Microglia and their important role in inflammation, MCs have been neglected. Further studies on MCs and their relation with Microglia as an inseparable inflammatory unit, may lead to a better understanding of AD and its progression and innovative therapeutic ways.