FIGURE 4.

Schematic diagram of AD pathogenesis. Several risk factors, such as aging, genetics, sleep deprivation, stress, diet, and head injury, can influence AD progression via chronic immune activation and cellular senescence. This, in turn, leads to aging‐associated chronic inflammatory responses, also known as inflammaging, which allows penetration of inflammatory molecules (pathogen‐ and/or damage‐associated molecular patterns, eg, lipopolysaccharide and HMGB1) through the BBB via glial senescence. In the brain, risk factors and inflammation impact neuronal homeostasis and induce Aβ and tau aggregation to form oligomers that cause neuronal insults, which further fuels brain inflammation. Additionally, disruption of the BBB facilitates the entry of peripheral inflammatory molecules and cells into the brain, which promotes gliosis and glial senescence followed by chronic brain inflammation. These events lead to the progression of AD pathology, neuronal and synaptic dysfunction, and cognitive decline. Aβ, amyloid beta; AD, Alzheimer's disease; BBB, blood‐brain barrier; SASP, senescence‐associated secretory phenotype.