G-protein coupled estrogen receptor 1, amyloid-β, and tau tangles in older adults

Oveisgharan, Shahram; Yu, Lei; de Paiva Lopes, Katia; Petyuk, Vladislav A.; Tasaki, Shinya; Vialle, Ricardo; Menon, Vilas; Wang, Yanling; De Jager, Philip L.; Schneider, Julie A.; Bennett, David A.

doi:10.1038/s42003-024-06272-9

Title: G-protein coupled estrogen receptor 1, amyloid-β, and tau tangles in older adults

Journal Article · 15 May 2024 · Communications Biology

DOI: https://doi.org/10.1038/s42003-024-06272-9 · OSTI ID:2446806

^[1];

^[1]; de Paiva Lopes, Katia ^[1];

^[2]; Tasaki, Shinya ^[1];

^[1];

^[3]; Wang, Yanling ^[1];

^[3]; Schneider, Julie A. ^[1]; Bennett, David A. ^[1]

Rush University Medical Center, Chicago, IL (United States)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Columbia University Irving Medical Center, New York, NY (United States)

Accumulation of amyloid-β (Aβ) and tau tangles are hallmarks of Alzheimer’s disease. Aβ is extracellular while tau tangles are typically intracellular, and it is unknown how these two proteinopathies are connected. Here, we use data of 1206 elders and test that RNA expression levels of GPER1, a transmembrane protein, modify the association of Aβ with tau tangles. GPER1 RNA expression is related to more tau tangles (p = 0.001). Moreover, GPER1 expression modifies the association of immunohistochemistry-derived Aβ load with tau tangles (p = 0.044). Similarly, GPER1 expression modifies the association between Aβ proteoforms and tau tangles: total Aβ protein (p = 0.030) and Aβ38 peptide (p = 0.002). Using single nuclei RNA-seq indicates that GPER1 RNA expression in astrocytes modifies the relation of Aβ load with tau tangles (p = 0.002), but not GPER1 in excitatory neurons or endothelial cells. We conclude that GPER1 may be a link between Aβ and tau tangles driven mainly by astrocytic GPER1 expression.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE; National Institute of Health (NIH)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2446806

Report Number(s):: PNNL-SA--202783

Journal Information:: Communications Biology, Journal Name: Communications Biology Journal Issue: 1 Vol. 7; ISSN 2399-3642

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: English

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