Immunohistochemical study of proteins related to the pathophysiology of Alzheimer's disease in the human retina of elderly patients without dementia.

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  • LIMEI LI
    Department of Psychiatry, Juntendo University School of Medicine
  • TAKAHASHI TADASHI
    Department of Psychiatry, Juntendo University School of Medicine
  • NAKAMURA SHINJI
    Division of Biomedical Imaging Research, Biomedical Research Center, Juntendo University Graduate School of Medicine
  • MURAKAMI AKIRA
    Department of Ophthalmology, Juntendo University School of Medicine
  • ARAI HEII
    Department of Psychiatry, Juntendo University School of Medicine

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Other Title
  • 非痴呆高齢者網膜におけるアルツハイマー病病態関連物質の発現に関する免疫組織化学的検討
  • ヒチホウ コウレイシャ モウマク ニ オケル アルツハイマービョウ ビョウタイ カンレン ブッシツ ノ ハツゲン ニ カンスル メンエキ ソシキ カガクテキ ケントウ

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Objective: The pathological features of Alzheimer's disease (AD) include neuritic plaques (NP) composed of amyloid-beta peptide (Aβ) fibrils, neurofibrillary tangles (NFT) of hyperphosphorylated Tau, and neurotransmitter deficits. Human retinal synapses directly associate with the central nervous system (CNS) through the optic nerve, and the bilateral optic nerves are both derived from the same origin, neural ectoderm. Therefore, it is possible that there would be neuropathological changes in the retina of AD patients similar to those in the CNS. As there are age-related changes observed in the retina, it would be important to investigate the location of proteins related to the neurodegeneration and pathophysiology of AD in the retina. In this study, we investigated the existence and expression pattern of AD-related neuropathological changes in the retina and optic nerve of elderly patients without dementia. Subjects and methods: Retinal samples of six individuals without dementia were obtained from the eye bank of Juntendo University hospital. The mean age ± SD was 68.3±6.1 years. By immunohistochemical analysis, the presence of ten kinds of proteins related to neurodegeneration and AD pathology (advanced glycation end-products, cathepsin D, amyloid β-precursor protein, ubiquitin, calretinin, nitrotyrosine, α-synuclein, PHF-Tau, Tau, single stranded DNA5) were detected using separate antibodies. Results: We found that PHF-Tau, an important component of amyloid β-precursor protein and a major component of NP and NFT, was strongly expressed in the retina except for single-stranded DNA. Other proteins also showed medium to strong signals with particular patterns. Conclusion: These findings demonstrate for the first time the location of proteins related to AD in the retina of elderly patients without dementia, indicating a relationship between the aging process and neurodegeneration in the human retina. Further neuropathological studies of the retina from both young patients without dementia and patients with AD should be investigated in the future.

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