Study Describes How Alzheimer’s and POAG Share Pathogenic Mechanisms

Glaucoma shares some pathogenic mechanisms with neurodegenerative diseases such as Alzheimer’s, and possibly psychiatric conditions like depression as well. This suggests a potential correlation between glaucoma and structural changes in the brain. Researchers in China, arguing  that a comprehensive understanding of the eye-brain axis could lead to more advanced treatments, recently conducted Mendelian randomization analysis to explore the causal relationship between glaucoma and brain function, specifically focusing on the brain’s cortical surface area and cortical thickness. They found that glaucoma-related functions might drive broad structural brain changes. They also uncovered similarities and differences between primary open-angle glaucoma (POAG) and Alzheimer’s, identifying significant and notable potential preclinical markers.  A recent study demonstrated that several brain cortical regions including visual and nonvisual ways where cortical surface area and cortical thickness were affected by glaucoma. Transneuronal degeneration may be one of the causes of cortical changes in the brain. Glaucoma involves transneuronal degeneration of the posterior structures along the central visual pathway. Photo: James L. Fanelli, OD. Click image to enlarge. “Brain magnetic resonance imaging of different functional regions may offer clues for early screening of high-risk populations for psychiatric and neurodegenerative disorders in glaucoma patients,” the study authors wrote in their paper, which was published in Medicine.To identify the causal relationship between glaucoma and brain cortical function, the researchers used six sets of genetic instruments indicating different aspects of glaucoma pathophysiology, including single nucleotide polymorphisms (SNPs) representing glaucoma. They also analyzed 34 regional cortical surface area and corneal thickness measurements.Due to data source constraints and the cross-sectional nature of the study, the researchers were only able to compare Alzheimer’s with glaucoma. As a result, they could not determine the temporal sequence or causal relationship between Alzheimer’s and glaucoma.The team identified significant associations between glaucoma and brain cortex regions, including the superior temporal sulcus, anterior cingulate, cuneus, entorhinal, inferior temporal and insula. They found about 18 overlapping genes between Alzheimer’s and POAG and identified 11 as most related to both conditions, including TSC2, MAGED4, LSS and DNM1.Genomic analysis revealed common functions in lipid metabolism, the mTOR pathway, endocytosis and phagocytosis. The study authors suggested that disruption of lipid metabolism homeostasis may serve as a common mechanism of degeneration in both glaucoma and Alzheimer’s, potentially acting as a bridge in the eye-brain axis.The mTOR signaling pathway plays a crucial role in coordinating various neuronal functions and maintaining neuronal homeostasis in the brain and retina. Abnormalities in the mTOR pathway can disrupt autophagic processes, leading to neurotoxic cell death. Damage to endocytosis and phagocytosis can also lead to retinal ganglion cell loss and neuronal degeneration, contributing to the development of neurodegenerative diseases. Anterograde transsynaptic degeneration is the process in which retinal degeneration causes subsequent degeneration of the posterior visual pathway. “On the one hand, the mechanism of transneuronal degeneration can be a contributing factor to defects in the visual pathway,” the researchers wrote. “On the other hand, nonvisual cognitive pathways were also influ­enced by POAG, like cingulate cortex, caudate nucleus, corpus callosum and claustrum. This might explain the emotion change in glaucoma patients.”The researchers advised caution in interpreting the findings and suggested that further studies with larger sample sizes and more precise measurements are necessary to validate these associations. Click here for the journal source. Chen X, Shi C, He M, Xia X. Novel insights into the relationship between glaucoma and brain diseases from the genetic to disease levels: a cross-sectional study. Medicine (Baltimore). 2025;104(38):e44416.  This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.