Innate Immune System and Inflammation in Alzheimer's Disease: From Pathogenesis to Treatment

Abstract

Immune activation and inflammation, likely triggered by amyloid-beta (Aβ) deposition, play a remarkable role in the pathogenesis of Alzheimer's disease (AD), which is the most frequent cause of dementia in the elderly. The principal cellular elements of the brain innate immune system likely to be involved in such processes are microglia. In an attempt to search for new disease-modifying drugs, the immune system has been addressed, with the aim of removing deposition of Aβ or tau by developing vaccines and humanized monoclonal antibodies. The aim of this review is to summarize the current evidence regarding the role played by microglia and inflammatory molecules in the pathogenesis of AD. In addition, we will discuss the main active and passive immunotherapeutic approaches.

Cardiovascular risk factors and future risk of Alzheimer’s disease

“…Astrocytes and microglia activate the neuronal immune system in response to pathogens such as infection and vascular pathology [125],[126]. Several studies showed that senile plaques in the brains of patients with AD and of AD transgenic mice models were surrounded by an increased number of activated microglia [127].…”

“…Several studies showed that senile plaques in the brains of patients with AD and of AD transgenic mice models were surrounded by an increased number of activated microglia [127]. Amyloid β also activates the neuronal immune system, and might cause a chronic inflammatory reaction that has a toxic effect on nerve cells [126]. Moreover, recent genetic studies have uncovered various genes for inflammation and immune response that seem to be associated with AD [128].…”

“…Moreover, recent genetic studies have uncovered various genes for inflammation and immune response that seem to be associated with AD [128]. However, there have been no major population-based cohort studies studying inflammation in AD, and trials studying the effect of immunotherapy on AD have not yet been successful [126]. Hence, further studies are required to elucidate the exact role of inflammation in AD.…”

Periodontal Disease as a Possible Risk Factor for Alzheimer’s Disease

“…There are various data on intravascular infiltration of periodontal disease-related bacteria and its spread to target organs thus far, but its mechanism of affecting diseases is not fully understood. On the other hand, the inflammatory response has been known to play a large role in the progression of cerebrovascular disorder and dementia, conditions that often occur in the elderly [8][9][10]; however, the effect of periodontal disease is not fully understood.…”

Folic acid supplementation improves cognitive function by reducing the levels of peripheral inflammatory cytokines in elderly Chinese subjects with MCI

“…Developing novel strategies to protect cognition in the elderly population is critical for managing the disease burden and cost of care1. The pathogenesis and progression of Alzheimer’s disease (AD) (the first cause of dementia) are associated with various inflammatory processes23. Indeed, inflammatory processes play at least some role in the pathology of AD and mild cognitive impairment (MCI)4, which represents an intermediate state between normal cognitive aging and dementia.…”