Usage Information
Citation Information: JCI Insight. 2025;10(22):e184041. https://doi.org/10.1172/jci.insight.184041.
Abstract
Alzheimer disease (AD) is characterized by plaques and tangles, including calcium dysregulation and glycated products produced by reactive carbonyl compounds. AD brains have increased glyoxalase I (GLO1), a major scavenger of inflammatory carbonyl compounds, at early, but not later, stages of disease. Calcium dysregulation includes calcium leak from phosphorylated ryanodine receptor 2 (pS2808-RyR2), seen in aged macaques and AD mouse models, but the downstream consequences of calcium leak remain unclear. Here, we show that chronic calcium leak is associated with increased GLO1 expression and activity. In macaques, we found age-related increases in GLO1 expression in the prefrontal cortex (PFC), correlating with pS2808-RyR2, and localized to dendrites and astrocytes. To examine the relationship between GLO1 and RyR2, we used S2808D-RyR2 mutant mice exhibiting chronic calcium leak through RyR2, and found increased GLO1 expression and activity in the PFC and hippocampus as early as 1 month and as late as 21 months of age, with a bell-shaped aging curve. These aged S2808D-RyR2 mice demonstrated impaired working memory. As with macaques, GLO1 was expressed in astrocytes and neurons. Proteomics data generated from S2808D-RyR2 synaptosomes confirmed GLO1 upregulation. Altogether, these data suggest potential association between GLO1 and chronic calcium leak, providing resilience in early stages of aging.
Authors
Elizabeth Woo, Dibyadeep Datta, Shveta Bathla, Hannah Beatty, Pinar Caglayan, Ashley Kristant Albizu, TuKiet T. Lam, Jean Kanyo, Mary Kate Joyce, Shannon Leslie, Stacy Uchendu, Jonathan DeLong, Qinyue Stacy Guan, Jiaxin Li, Efrat Abramson, Alison L. Herman, Dawson Cooper, Pawel Licznerski, Tamas L. Horvath, Elizabeth A. Jonas, Angus C. Nairn, Amy F.T. Arnsten, Lauren H. Sansing
Usage data is cumulative from October 2025 through December 2025.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,135 | 2 |
| 386 | 0 | |
| Figure | 204 | 0 |
| Table | 5 | 0 |
| Supplemental data | 380 | 0 |
| Citation downloads | 71 | 0 |
| Totals | 2,181 | 2 |
| Total Views | 2,183 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
