Levothyroxine (a drug for hypothyroidism) is associated with a decreased risk of AD in patients with neuroinflammation-related conditions, but have a neutral association with AD in matched individuals without the corresponding conditions (Figures 3A). Levothyroxine demonstrates potential anti-inflammatory effect in clinical studies and AD mouse models.26, 27 Hypothyroidism can be treated by levothyroxine. Additionally hypothyroidism is related to the development of AD and AUD,28, 29 and the progression of hemorrhagic stroke (HS) and traumatic brain injury (TBI).30, 31 However, drug responses of levothyroxine in AD in patients with neuroinflammation-related conditions are largely unknown. We find consistent results between levothyroxine and AD in all neuroinflammation-related cohorts and all non-neuroinflammation-related cohorts (Figure 3A), which suggesting a potential beneficial drug-host (i.e., levothyroxine-neuroinflammation) interaction effect in AD.
