Introduction The pathological formation of amyloid plaques and the sub- sequent aggregation of hyperphosphorylated tau into neu- rofibrillary tangles are thought to be the primary force driving the pathogenesis of Alzheimer’s disease. An analy- sis of existing studies has suggested that -amyloid 1–42 (A42) and tau in the cerebrospinal fluid (CSF) may be the most promising biomarkers for a sensitive and specific CSF diagnosis of Alzheimer’s disease. 1 That analysis revealed that A42 decreased and tau increased in the CSF from Alzheimer’s disease patients in comparison with healthy subjects. We were interested in a recent report demonstrating a high occurrence rate of glaucoma in patients with Alzheimer’s disease. 2,3 McKinnon et al. 4 have reported that rat retinal ganglion cells subjected to chronic ocular hyper- tension exhibit abnormal processing of amyloid precursor protein, leading to the production of -amyloid. Johnson et al. 5 have reported that A-peptide is localized at sites of drusen deposition and may contribute to atrophy of the retinal pigment epithelium and the pathogenesis of some retinal diseases. More recently, an association between diabetes mellitus and an increased risk of developing Alzheimer’s disease has been suggested, 6 and, moreover, tau hyperphosphorylation has been observed in a central nervous system-specific insulin receptor of knockout mice. 7 Jpn J Ophthalmol 2005;49:106–108 DOI 10.1007/s10384-004-0156-x © Japanese Ophthalmological Society 2005 LABORATORY INVESTIGATION Vitreous Fluid Levels of -Amyloid (1–42) and Tau in Patients with Retinal Diseases Shinji Yoneda 1 , Hideaki Hara 2 , Akira Hirata 3 , Mikiko Fukushima 3 , Yasuya Inomata 3 , and Hidenobu Tanihara 3 1 Research and Development Center, Santen Pharmaceutical Company, Ltd., Ikoma, Japan; 2 Department of Biofunctional Molecules, Gifu Pharmaceutical University, Gifu, Japan; 3 Department of Ophthalmology and Visual Science, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan Abstract Purpose: A decrease in -amyloid 1–42 (A42) and an increase in tau in the cerebrospinal fluid are reported to be characteristic phenomena in Alzheimer’s disease patients.To test the idea that A42 and tau con- tribute to the development of retinal diseases, we measured A42 and tau concentrations in the vitre- ous fluid from patients with macular hole (n = 13), diabetic retinopathy (n = 15), or glaucoma concurrent with other ocular diseases (n = 8). Methods: Vitreous samples were collected from patients who underwent vitrectomy, and sensitive and specific enzyme-linked immunosorbent assays were used to determine the concentrations of A42 and tau. Results: By comparison with the levels in the control macular-hole patients (33.9  7.1 pg/ml for A42; 3.3  3.2 pg/ml for tau), there was a significant decrease in the A42 level and a significant increase in the tau level in patients with diabetic retinopathy (1.8  1.9 pg/ml for A42, P = 0.002; 153.7  71.6 pg/ml for tau, P = 0.041) or glaucoma concurrent with other ocular diseases (2.8  1.8 pg/ml for A42, P = 0.006; 113.6  43.1 pg/ml for tau, P = 0.023). Conclusions: Our findings indicate the possibility of a role for A42 and tau in the pathogenesis of some retinal diseases. Jpn J Ophthalmol 2005;49:106–108 © Japanese Ophthalmological Society 2005 Key Words: -amyloid, diabetic retinopathy, glaucoma, tau, vitreous fluid Received: March 4, 2004 / Accepted: August 5, 2004 Correspondence and reprint requests to: Hideaki Hara, Department of Biofunctional Molecules, Gifu Pharmaceutical University, 1-5-90 Mitahora-higashi, Gifu 502-8585, Japan e-mail: hidehara@gifu-pu.ac.jp