For years, glaucoma has been framed primarily as a pressure disease — yet its behavior often defies that narrative. Patients with normal-tension glaucoma progress despite “acceptable” intraocular pressure (IOP), and others with pseudoexfoliation progress rapidly even with aggressive pressure control. A growing body of evidence suggests that glaucoma may share surprising molecular territory with Alzheimer’s disease (AD). The Scientific Reports study, conducted by Japanese researchers at the Ohashi Eye Center, brings this convergence into focus by examining a biomarker that has dominated neurodegenerative research: amyloid-β (Aβ).
Aβ peptides — long implicated in AD pathogenesis — have been detected in human retina and optic nerve tissue. Their presence raises the possibility that glaucomatous neurodegeneration might involve similar molecular stressors. Yet until now, few studies have assessed whether Aβ accumulates in living human eyes in a way that correlates with disease severity.
The study authors conducted a prospective study evaluating Aβ₁₋₄₀ and Aβ₁₋₄₂ concentrations in the aqueous humor of patients undergoing cataract or glaucoma surgery. Four clinical groups were compared: cataract (controls), glaucoma, pseudoexfoliation syndrome (PEX), and exfoliation glaucoma (ExG). Retinal nerve fiber layer thickness (RNFLT) served as the structural index of damage.
The study data revealed a consistent pattern:
Aβ₁₋₄₀ and Aβ₁₋₄₂ were significantly elevated in both PEX and ExG compared with controls.
Exfoliation glaucoma showed the highest concentrations of all groups.
Aβ₁₋₄₀ and Aβ₁₋₄₂ were strongly correlated across all groups, suggesting common regulatory mechanisms.
Interestingly, these elevations were independent of age and preoperative IOP, emphasizing that Aβ is not simply a consequence of higher pressure or older age.
The most clinically salient finding lies in the relationship between Aβ and RNFLT. In both glaucoma and exfoliation glaucoma, higher Aβ levels correlated with thinner RNFL, particularly for Aβ₁₋₄₀. This suggests a potential mechanistic link between Aβ toxicity and retinal ganglion cell loss.
The researchers note that the absolute Aβ burden in aqueous humor is not trivial: calculated molar quantities are comparable to doses that induce retinal ganglion cell apoptosis in animal models.
It should be noted that the study does not claim that Aβ causes glaucoma — but it clearly strengthens the argument that glaucoma and AD share convergent neurodegenerative pathways, raising the possibility that Aβ could serve as a biomarker for disease activity or progression, as well as the idea that targeting Aβ pathways could one day complement pressure-lowering therapy.
