Kim, Dong Kyu Choi, Hyunjung Lee, Woochan Choi, Hayoung Hong, Seok Beom Jeong, June-Hyun Han, Jihui Han, Jong Won Ryu, Hoon Kim, Jong-Il Mook-Jung, Inhee 2024-04-18T05:30:30Z 2024-04-18T05:30:30Z 2024-04-18 2024-03 https://pubs.kist.re.kr/handle/201004/149667 Thyroid hormone (TH) imbalance is linked to the pathophysiology of reversible dementia and Alzheimer's disease (AD). It is unclear whether tissue hypothyroidism occurs in the AD brain and how it affects on AD pathology. We find that decreased iodothyronine deiodinase 2 is correlated with hippocampal hypothyroidism in early AD model mice before TH alterations in the blood. TH deficiency leads to spontaneous activation of microglia in wild-type mice under nonstimulated conditions, resulting in lowered innate immune responses of microglia in response to inflammatory stimuli or amyloid-beta. In AD model mice, TH deficiency aggravates AD pathology by reducing the disease-associated microglia population and microglial phagocytosis. We find that TH deficiency reduces microglial ecto-5 '-nucleotidase (CD73) and inhibition of CD73 leads to impaired innate immune responses in microglia. Our findings reveal that TH shapes microglial responses to inflammatory stimuli including amyloid-beta, and brain hypothyroidism in early AD model mice aggravates AD pathology by microglial dysfunction. English American Association for the Advancement of Science Brain hypothyroidism silences the immune response of microglia in Alzheimer's disease animal model Article 10.1126/sciadv.adi1863 1 Science Advances, v.10, no.11 Science Advances 10 11 Y scie scopus 001190089500009 2-s2.0-85188200866 Multidisciplinary Sciences Science & Technology - Other Topics Article METAANALYSIS DYSFUNCTION EXPRESSION THYROID-HORMONE AMYLOID-BETA