title: Estrogen receptor-α is localized to neurofibrillary tangles in Alzheimer's disease.
abstract: The female predominance for developing Alzheimer disease (AD) suggests the involvement of gender specific factor(s) such as a reduced estrogen-estrogen receptor signaling in the pathogenesis of AD. The potential role of ERα in AD pathogenesis has been explored by several groups with mixed results. We revisited this issue of expression and distribution of ERα in AD brain using a specific ERα antibody. Interestingly, we found that ERα co-localized with neurofibrillary pathology in AD brain and further demonstrated that ERα interacts with tau protein in vivo. Immunoprecipitaion experiments found increased ERα-tau interaction in the AD cases, which may account for ERα being sequestered in neuronal tau pathology. Indeed, tau overexpression in M17 cells leads to interruption of estrogen signaling. Our data support the idea that sequestration of ERα by tau pathology underlies the loss of estrogen neuroprotection during the course of AD.
authors.affiliation: Department of Neurology, the second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.|Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.|Department of Neurosurgery, Chengdu first people's Hospital, Chengdu, The People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Sirui
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Siedlak
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA.
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Xinglong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D015398:Signal Transduction; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C054369:MAPT protein, human; D016875:tau Proteins
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