1. G-protein coupled estrogen receptor 1, amyloid-β, and tau tangles in older adults.
- Author
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Oveisgharan S, Yu L, de Paiva Lopes K, Petyuk VA, Tasaki S, Vialle R, Menon V, Wang Y, De Jager PL, Schneider JA, and Bennett DA
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Male, Astrocytes metabolism, Neurofibrillary Tangles metabolism, Neurofibrillary Tangles pathology, Alzheimer Disease metabolism, Alzheimer Disease genetics, Amyloid beta-Peptides metabolism, Amyloid beta-Peptides genetics, Receptors, Estrogen metabolism, Receptors, Estrogen genetics, Receptors, G-Protein-Coupled metabolism, Receptors, G-Protein-Coupled genetics, tau Proteins metabolism, tau Proteins genetics
- Abstract
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., (© 2024. The Author(s).)
- Published
- 2024
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