Estrogen receptor-α is localized to neurofibrillary tangles in Alzheimer's disease

Chunyu Wang, Fan Zhang, Sirui Jiang, Sandra L. Siedlak, Lu Shen, George Perry, Xinglong Wang, Beisha Tang, Xiongwei Zhu

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number20352
JournalScientific reports
StatePublished - Feb 3 2016
Externally publishedYes

ASJC Scopus subject areas

  • General

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