Neuroinflammation: A Possible Link Between Chronic Vascular Disorders and Neurodegenerative Diseases

Abstract

Various age-related diseases involve systemic inflammation, i.e. a stereotyped series of acute immune system responses, and aging itself is commonly associated with low-grade inflammation or inflamm'aging. Neuroinflammation is defined as inflammation-like processes inside the central nervous system, which this review discusses as a possible link between cardiovascular disease-related chronic inflammation and neurodegenerative diseases. To this aim, neuroinflammation mechanisms are first summarized, encompassing the cellular effectors and the molecular mediators. A comparative survey of the best-known physiological contexts of neuroinflammation (neurodegenerative diseases and transient ischemia) reveals some common features such as microglia activation. The recently published transcriptomic characterizations of microglia have pointed a marker core signature among neurodegenerative diseases, but also unraveled the discrepancies with neuroinflammations related with acute diseases of vascular origin. We next review the links between systemic inflammation and neuroinflammation, beginning with molecular features of respective pro-inflammatory cells, i.e. macrophages and microglia. Finally, we point out a gap of knowledge concerning the atherosclerosis-related neuroinflammation, which is for the most surprising given that atherosclerosis is established as a major risk factor for neurodegenerative diseases.

Keywords: Alzheimer’s disease; astrocytes; inflammation; ischemia-reperfusion; macrophages; microglia; neuroinflammation.

FIGURE 1

Cellular mechanisms of inflammation and neuroinflammation: a schematic picture. Immune and neural effector cells of inflammation and neuroinflammation are represented in horizontal rows. Healthy and pathological phenotypes are categorized in columns. Plain vs. dashed arrows indicate demonstrated vs. hypothetical switches from one phenotype to another. Acute vs. chronic diseases are indicated in italic. DAM, disease-associated microglia.