HMGB1‐Mediated Senescence and Brain Inflammation Contributes to Cognitive Dysfunctions

High mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein, which is excessively released by glial cells during aging and Alzheimer’s Disease (AD). The extracellular HMGB1 serves as a key initiator of neuroinflammation, which is linked to exacerbated cognitive impairments in AD. Importantly, aging ‐ the strongest risk factor for AD is characterized by a chronic, low‐grade inflammation known as inflammaging. Evidence suggests that senescent cells (SC) accumulate with aging and are characterized by an apoptosis‐resistant, arrested cell cycle with a distinct “inflammatory” phenotype also known as senescence‐associated secretory phenotype (SASP). However, the precise etiology of inflammaging in tauopathies remain largely unknown.