Targeting Microglia; A therapeutic approach against Alzheimer’s disease

Alzheimer’s disease (AD) is responsible for many cases of dementia, characterized by neuroinflammation and increased microglial activation. The overall aim of this literature study was to analyze if microglia can be used as a therapeutic target against AD. In order to answer this question, the focus lay on the role of microglia in the brain and its relation with AD. Since AD is mostly diagnosed in a later life stage, ageing is also included. Within AD, formation of amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs) leads to chronic activation of microglia and the transition into the pro-inflammatory M1 phenotype. Activation of these microglia results in inflammation, leading to neuronal damage. During AD progression the anti-inflammatory M2 microglia, become dysfunctional and are replaced by pro-inflammatory M1 microglia, creating further damage accompanied by cognitive impairments. Upon age, microglial develop a highly sensitive primed phenotype. Activation of this phenotype leads to an uncontrolled pro-inflammatory immune response with a decreased capacity of chemotaxis and phagocytosis. For drug design, the focus could lie on restoring the balance between the M1 and M2 microglia, regulation of the neuroinflammation by inhibition or stimulation of receptors and cytokines, prevention of primed microglia and the elimination of the neuroinflammatory stimuli.