Alzheimer's disease (AD) accounts for up to 80% of all dementia cases. The striking similarity in cognitive decline symptoms between AD and hypothyroidism is notable observation with numerous reports emphasizing thyroid hormone imbalance in AD patients. However, the precise mechanism by which thyroid hormone deficiency induces pathological changes remains elusive. This study aims to shed light on the reciprocal relation between AD pathology and hypothyroidism in the brain. Our research demonstrates that AD pathology triggers a deficiency of active thyroid hormone within the brain. Notably, thyroid hormone deficiency hampers the immune response of microglia, brain-resident immune cells responsible for clearing pathological protein aggregates. Consequently, this impairment exacerbates the accumulation of beta-amyloid and phosphorylated tau, hallmark features of AD. This study advances our understanding of altered thyroid hormone metabolism in the brain of AD. Furthermore, supplementing deficient thyroid hormone has provided a new perspective for treating AD, focusing on preserving the immune function of microglia.

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