Alzheimer's disease pathophysiology in the Retina,Progress in Retinal and Eye Research

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Alzheimer's disease pathophysiology in the Retina
Progress in Retinal and Eye Research ( IF 18.6 ) Pub Date : 2024-05-15 , DOI: 10.1016/j.preteyeres.2024.101273
Bhakta Prasad Gaire ₁ , Yosef Koronyo ₁ , Dieu-Trang Fuchs ₁ , Haoshen Shi ₁ , Altan Rentsendorj ₁ , Ron Danziger ₂ , Jean-Philippe Vit ₁ , Nazanin Mirzaei ₁ , Jonah Doustar ₁ , Julia Sheyn ₁ , Harald Hampel ₃ , Andrea Vergallo ₃ , Miyah R Davis ₁ , Ousman Jallow ₁ , Filippo Baldacci ₄ , Steven R Verdooner ₅ , Ernesto Barron ₆ , Mehdi Mirzaei ₇ , Vivek K Gupta ₇ , Stuart L Graham ₈ , Mourad Tayebi ₉ , Roxana O Carare ₁₀ , Alfredo A Sadun ₆ , Carol A Miller ₁₁ , Oana M Dumitrascu ₁₂ , Shouri Lahiri ₂ , Liang Gao ₁₃ , Keith L Black ₁ , Maya Koronyo-Hamaoui ₁₄

Affiliation

Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Sorbonne University, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France.
Sorbonne University, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France; Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy.
NeuroVision Imaging Inc., Sacramento, CA, USA.
Department of Ophthalmology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA; Doheny Eye Institute, Los Angeles, CA, USA.
Department of Clinical Medicine, Health and Human Sciences, Macquarie Medical School, Macquarie University, Sydney, NSW, Australia.
Department of Clinical Medicine, Health and Human Sciences, Macquarie Medical School, Macquarie University, Sydney, NSW, Australia; Department of Clinical Medicine, Macquarie University, Sydney, NSW, Australia.
School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.
Department of Clinical Neuroanatomy, University of Southampton, Southampton, UK.
Department of Pathology Program in Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA.
Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.
Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences, Division of Applied Cell Biology and Physiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks of AD, including amyloid β-protein (Aβ) deposits and abnormal tau protein isoforms, in the retinas of AD patients and animal models. Moreover, structural and functional vascular abnormalities such as reduced blood flow, vascular Aβ deposition, and blood-retinal barrier damage, along with inflammation and neurodegeneration, have been described in retinas of patients with mild cognitive impairment and AD dementia. Histological, biochemical, and clinical studies have demonstrated that the nature and severity of AD pathologies in the retina and brain correspond. Proteomics analysis revealed a similar pattern of dysregulated proteins and biological pathways in the retina and brain of AD patients, with enhanced inflammatory and neurodegenerative processes, impaired oxidative-phosphorylation, and mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific amyloid deposits, as well as vasculopathy and neurodegeneration in the retina of living AD patients, suggesting alterations at different disease stages and links to brain pathology. Current and exploratory ophthalmic imaging modalities, such as optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, and hyperspectral imaging, may offer promise in the clinical assessment of AD. However, further research is needed to deepen our understanding of AD's impact on the retina and its progression. To advance this field, future studies require replication in larger and diverse cohorts with confirmed AD biomarkers and standardized retinal imaging techniques. This will validate potential retinal biomarkers for AD, aiding in early screening and monitoring.

中文翻译：

视网膜阿尔茨海默病的病理生理学

视网膜是一种新兴的中枢神经系统目标，可用于阿尔茨海默病 (AD) 的无创诊断和跟踪。研究已经确定了 AD 患者和动物模型视网膜中 AD 的病理特征，包括 β 淀粉样蛋白 (Aβ) 沉积和异常 tau 蛋白亚型。此外，轻度认知障碍和 AD 痴呆患者的视网膜存在结构和功能性血管异常，例如血流减少、血管 Aβ 沉积和血-视网膜屏障损伤，以及炎症和神经变性。组织学、生化和临床研究表明，视网膜和大脑中 AD 病理的性质和严重程度是一致的。蛋白质组学分析揭示了 AD 患者视网膜和大脑中类似的蛋白质失调和生物途径模式，炎症和神经退行性过程增强，氧化磷酸化受损，线粒体功能障碍。值得注意的是，研究成像技术现在可以检测 AD 特异性淀粉样蛋白沉积物，以及活体 AD 患者视网膜中的血管病变和神经变性，表明不同疾病阶段的变化以及与大脑病理学的联系。当前和探索性眼科成像模式，例如光学相干断层扫描 (OCT)、OCT 血管造影、共焦扫描激光检眼镜和高光谱成像，可能为 AD 的临床评估带来希望。然而，我们还需要进一步的研究来加深我们对 AD 对视网膜的影响及其进展的理解。为了推进这一领域的发展，未来的研究需要在更大、更多样化的队列中进行复制，并使用已确认的 AD 生物标志物和标准化的视网膜成像技术。这将验证 AD 的潜在视网膜生物标志物，有助于早期筛查和监测。

更新日期：2024-05-15

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