Therapeutic Targets in Innate Immunity to Tackle Alzheimer's Disease

There is an urgent need for effective disease-modifying therapeutic interventions for Alzheimer's disease (AD)-the most prevalent cause of dementia with a profound socioeconomic burden. Most clinical trials targeting the classical hallmarks of this disease-beta-amyloid plaques and neurofibrillary tangles-failed, showed discrete clinical effects, or were accompanied by concerning side effects. There has been an ongoing search for novel therapeutic targets. Neuroinflammation, now widely recognized as a hallmark of all neurodegenerative diseases, has been proven to be a major contributor to AD pathology. Here, we summarize the role of neuroinflammation in the pathogenesis and progression of AD and discuss potential targets such as microglia, TREM2, the complement system, inflammasomes, and cytosolic DNA sensors. We also present an overview of ongoing studies targeting specific innate immune system components, highlighting the progress in this field of drug research while bringing attention to the delicate nature of innate immune modulations in AD.