Ophthalmological markers of Alzheimer's disease
https://doi.org/10.33667/2078-5631-2022-1-47-53
Abstract
Alzheimer's disease (AD) is the most common neurodegenerative disease-causing dementia. The severity of symptoms determines the diagnosis of AD, although an accurate diagnosis can only be made postmortem. Neuropsychological testing is the «gold standard» for early diagnosis of AD, but is time-consuming, does not allow a complete diagnosis with complete accuracy, is highly dependent on the correctness of the tests, and is rather an adjunct to the examination of the patient. Lumbar puncture and positron emission tomography are not available for routine screening of the population. Because the eye is an extension of the central nervous system, the study of its changes may lead to the development of a number of non-invasive differential diagnostic tests to identify patients with AD at an early stage. In recent years, the advent of quantifiable high-resolution imaging techniques that are non-invasive, rapid, and widely available has opened up a new field of ocular-neural imaging. In this paper, we review current foreign and domestic studies of some ocular biomarkers and the methods that could potentially be used in the early diagnosis of Alzheimer's disease.
About the Authors
V. Yu. Lobzin
North-Western State Medical University n. a. I. I. Mechnikov; Children's Research and Clinical Centre for Infectious Diseases; Military Medical Academy n. a. S. M. Kirov
Russian Federation
Russian Federation
Lobzin Vladimir Yu., DM Sci (habil.), professor, professor at Dept of Neurology n. a. acad. S. N. Davidenkov, senior researcher at Dept of Neuroinfections and Organic Pathology of Nervous System, professor at Dept of Nervous Diseases
Saint Petersburg
D. S. Maltsev
Military Medical Academy n. a. S. M. Kirov
Russian Federation
Russian Federation
Maltsev Dmitrii S., DM Sci (habil.), assistant professor, assistant professor at Ophthalmology Dept, head of Laser Dept of Ophthalmology Clinic
Saint Petersburg
E. S. Strumentova
North-Western State Medical University n. a. I. I. Mechnikov
Russian Federation
Russian Federation
Strumentova Elena S., neurologist, 1st year postgraduate student of Dept of Neurology n. a. acad. S. N. Davidenkov
Saint Petersburg
M. A. Burnasheva
Military Medical Academy n. a. S. M. Kirov
Russian Federation
Russian Federation
Burnasheva Maria A., ophthalmologist of Ophthalmology Dept
Saint Petersburg
S. S. Cheremisin
North-Western State Medical University n. a. I. I. Mechnikov
Russian Federation
Russian Federation
Cheremisin Sergey S., 1st year resident of Dept of Neurology n. a. acad. S. N. Davidenkov
Saint Petersburg
References
1. Jack C. R. et al. A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016; 87 (5): 539–47. DOI: 10.1212/WNL.0000000000002923.
2. Wagner S. K., Fu D. J., Faes L. et al. Insights into Systemic Disease through Retinal Imaging-Based Oculomics [published correction appears in Transl Vis Sci Technol. Transl Vis Sci Technol. 2020; 9 (2): 6. DOI: 10.1167/tvst.9.2.6.
3. Boerger M., Funke S., Leha A., et al. Proteomic analysis of tear fluid reveals disease-specific patterns in patients with Parkinson's disease – A pilot study. Parkinsonism Relat Disord. 2019; 63: 3–9. DOI: 10.1016/j.parkreldis.2019.03.001.
4. Pieragostino D., Lanuti P., Cicalini.I, et al. Proteomics characterization of extracellular vesicles sorted by flow cytometry reveals a disease-specific molecular cross-talk from cerebrospinal fluid and tears in multiple sclerosis. J Proteomics. 2019; 204: 103403. DOI: 10.1016/j.jprot.2019.103403.
5. Kenny A. Proteins and microRNAs are differentially expressed in tear fluid from patients with Alzheimer's disease. Scientific reports. 2019; 9 (1). 15437. DOI: 10.1038/s41598–019–51837-y.
6. Moreau K. L., King J. A. Protein misfolding and aggregation in cataract disease and prospects for prevention. Trends Mol Med. 2012; 18 (5): 273–282. DOI: 10.1016/j.molmed.2012.03.005.
7. Gijs M., Nuijts R. M., Ramakers I. et al. Differences in tear protein biomarkers between patients with Alzheimer’s disease and controls. Investig. Ophthalmol. 2019; 60 (9): 1744.
8. Lim JK, Li QX, He Z et al. The Eye as a Biomarker for Alzheimer's Disease. Front Neurosci. 2016; 10: 536. DOI: 10.3389/fnins.2016.00536.
9. Wang Y.-R. et al. High-Sensitivity and Trace-Amount Specimen Electrochemical Sensors for Exploring the Levels of β-Amyloid in Human Blood and Tears. Analytical chemistry. 2021; 93 (22): 8099–8106. DOI: 10.1021/acs.analchem.0c04980.
10. Karki H. P. et al. Advances in the development paradigm of biosample-based biosensors for early ultrasensitive detection of Alzheimer's disease. Journal of nanobiotechnology. 2021. 19 (1): 72. DOI: 10.1186/s12951–021–00814–7.
11. Dehghani C. et al. Ocular Biomarkers of Alzheimer's Disease: The Role of Anterior Eye and Potential Future Directions. Investigative ophthalmology & visual science. 2018. 59 (8): 3554–3563. DOI: 10.1167/iovs.18–24694.
12. Dehghani C. et al. Morphometric Changes to Corneal Dendritic Cells in Individuals with Mild Cognitive Impairment. Frontiers in neuroscience. 2020; 14: 556137. DOI: 10.3389/fnins.2020.556137.
13. Al-Janahi E. et al. Corneal Nerve and Brain Imaging in Mild Cognitive Impairment and Dementia. Journal of Alzheimer's disease. 2020. 77 (4): 1533–1543. DOI: 10.3233/JAD-200678.
14. Tavakoli M. et al. Corneal confocal microscopy: a novel non-invasive test to diagnose and stratify the severity of human diabetic neuropathy. Diabetes care. 2010; 33 (8): 1792–1797. DOI: 10.2337/dc10–0253.
15. Campagnolo M. et al. Corneal confocal microscopy in patients with oxaliplatin-induced peripheral neuropathy. Journal of the peripheral nervous system: JPNS Vol. 18, 3 (2013): 269–71. DOI: 10.1111/jns5.12036.
16. Ponirakis G. et al. Association of corneal nerve fiber measures with cognitive function in dementia. Annals of clinical and translational neurology Vol. 6, 4. 689–697. 2 Mar. 2019, DOI: 10.1002/acn3.746.
17. Singh A. K., Shilpa V. Use of ocular biomarkers as a potential tool for early diagnosis of Alzheimer's disease. Indian journal of ophthalmology Vol. 68, 4 (2020): 555–561. DOI: 10.4103/ijo.IJO_999_19.
18. Frost S. M. et al. Pupil response biomarkers distinguish amyloid precursor protein mutation carriers from non-carriers. Current Alzheimer research Vol. 10, 8 (2013): 790–6. DOI: 10.2174/15672050113109990154.
19. Forrester J. V., Dick A. D., McMenamin P.G. et al. The Eye: Basic Sciences in Practice, 2016.
20. Goldstein L. E. et al. Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease. Lancet (London, England) Vol. 361, 9365 (2003): 1258–65. DOI: 10.1016/S0140–6736(03)12981–9.
21. Moncaster J. A. et al. Alzheimer's disease amyloid-beta links lens and brain pathology in Down syndrome. PloS one Vol. 5, 5 e10659. 20 May. 2010, DOI: 10.1371/journal.pone.0010659.
22. Jun G. et al. δ-Catenin is genetically and biologically associated with cortical cataract and future Alzheimer-related structural and functional brain changes. PloS one vol. 7, 9 (2012): e43728. DOI: 10.1371/journal.pone.0043728.
23. Kerbage C. et al. Alzheimer's disease diagnosis by detecting exogenous fluorescent signal of ligand bound to Beta amyloid in the lens of human eye: an exploratory study. Frontiers in Neurology Vol. 4, 62. 27 May. 2013, DOI: 10.3389/fneur.2013.00062.
24. Kerbage C. et al. Detection of Amyloid β Signature in the Lens and Its Correlation in the Brain to Aid in the Diagnosis of Alzheimer's Disease. American Journal of Alzheimer's disease and other dementias Vol. 30, 8 (2015): 738–45. DOI: 10.1177/1533317513520214.
25. Michael R. Absence of amyloid-beta in lenses of Alzheimer patients: a confocal Raman microspectroscopic study. Experimental Eye Research Vol. 119 (2014): 44–53. DOI: 10.1016/j.exer.2013.11.016.
26. Williams E. A. et al. Absence of Alzheimer Disease Neuropathologic Changes in Eyes of Subjects with Alzheimer Disease. Journal of neuropathology and experimental neurology Vol. 76, 5 (2017): 376–383. DOI: 10.1093/jnen/nlx020.
27. Yu T. C., Okamura R. Quantitative study of characteristic aqueous humor transferrin, serum transferrin and desialized serum transferrin in aqueous humor. Japanese Journal of Ophthalmology Vol. 32, 3 (1988): 268–74.
28. Wright L. M. et al. Association of Cognitive Function with Amyloid-β and Tau Proteins in the Vitreous Humor. Journal of Alzheimer's Disease: JAD Vol. 68, 4 (2019): 1429–1438. DOI: 10.3233/JAD-181104.
29. Subramanian M. L. et al. Neurofilament light chain in the vitreous humor of the eye. Alzheimer's Research & Therapy Vol. 12, 1 111. 17 Sep. 2020, DOI: 10.1186/s13195–020–00677–4.
30. Lee C. S. et al. Associations between recent and established ophthalmic conditions and risk of Alzheimer's disease. Alzheimer's & dementia: the Journal of the Alzheimer's Association Vol. 15, 1 (2019): 34–41. DOI: 10.1016/j.jalz.2018.06.2856.
31. Lee C. S. et al. Ophthalmology-Based Neuropathology Risk Factors: Diabetic Retinopathy is Associated with Deep Microinfarcts in a Community-Based Autopsy Study. Journal of Alzheimer's disease: JAD Vol. 68, 2 (2019): 647–655. DOI: 10.3233/JAD-181087.
32. Xiao-He H. et al. Association between glaucoma and the risk of Alzheimer's disease: A systematic review of observational studies. Acta Ophthalmologica Vol. 97, 7 (2019): 665–671. DOI: 10.1111/aos.14114.
33. Ledig C. et al. Structural brain imaging in Alzheimer's disease and mild cognitive impairment: biomarker analysis and shared morphometry database. Scientific reports Vol. 8,1 11258. 26 Jul. 2018, DOI: 10.1038/s41598–018–29295–9.
34. Budenz D. L. et al. Determinants of normal retinal nerve fiber layer thickness measured by Stratus OCT. Ophthalmology Vol. 114, 6 (2007): 1046–52. DOI: 10.1016/j.ophtha.2006.08.046.
35. Kwon J. Y. et al. Analysis of the Retinal Nerve Fiber Layer Thickness in Alzheimer Disease and Mild Cognitive Impairment. Korean Journal of Ophthalmology: KJO Vol. 31, 6 (2017): 548–556. DOI: 10.3341/kjo.2016.0118.
36. Doustar J. et al. Optical Coherence Tomography in Alzheimer's Disease and Other Neurodegenerative Diseases. Frontiers in neurology Vol. 8 701. 19 Dec. 2017, DOI: 10.3389/fneur.2017.00701.
37. Grimaldi A. et al. Inflammation, neurodegeneration and protein aggregation in the retina as ocular biomarkers for Alzheimer's disease in the 3xTg-AD mouse model. Cell Death & Disease Vol. 9, 6 685. 7 Jun. 2018, DOI: 10.1038/s41419–018–0740–5.
38. Koronyo-Hamaoui M. et al. “Identification of amyloid plaques in retinas from Alzheimer's patients and non-invasive in vivo optical imaging of retinal plaques in a mouse model.” Neuro Image Vol. 54 Suppl 1 (2011): S 204–17. DOI: 10.1016/j.neuroimage.2010.06.020.
39. Jha N. N. et al. Effect of curcumin analogs onα-synuclein aggregation and cytotoxicity. Scientific Reports Vol. 6 28511. 24 Jun. 2016, DOI: 10.1038/srep28511.
40. den Haan J. et al. Different curcumin forms selectively bind fibrillar amyloid beta in post mortem Alzheimer's disease brains: Implications for in-vivo diagnostics. Acta Neuropathologica Communications Vol. 6, 1 75. 9 Aug.
41. Asanad S. et al. The Retina in Alzheimer's Disease: Histomorphometric Analysis of an Ophthalmologic Biomarker. Investigative Ophthalmology & Visual Science Vol. 60, 5 (2019): 1491–1500. DOI: 10.1167/iovs.18–25966.
42. Cunha J. P. et al. OCT in Alzheimer's disease: thinning of the RNFL and superior hemiretina. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie vol. 255, 9 (2017): 1827–1835. DOI: 10.1007/s00417–017–3715–9.
43. van de Kreeke J. A. et al. “Optical coherence tomography angiography in preclinical Alzheimer's disease.” The British Journal of Ophthalmology Vol. 104, 2 (2020): 157–161. DOI: 10.1136/bjophthalmol-2019–314127.
44. Zabel P. et al. Peripapillary Retinal Nerve Fiber Layer Thickness in Patients with Alzheimer's Disease: A Comparison of Eyes of Patients with Alzheimer's Disease, Primary Open-Angle Glaucoma, and Preperimetric Glaucoma and Healthy Controls.” Medical science monitor: International Medical Journal of Experimental and Clinical Research Vol. 25 1001–1008. 5 Feb. 2019, DOI: 10.12659/MSM.914889.
45. Kirbas S. et al. Retinal nerve fiber layer thickness in patients with Alzheimer disease. Journal of Neuro-Ophthalmology: The Official Journal of the North American Neuro-Ophthalmology Society Vol. 33, 1 (2013): 58–61. DOI: 10.1097/WNO.0b013e318267fd5f.
46. Liu D., Zhang L., Li Z. et al. (2015). Thinner changes of the retinal nerve fiber layer in patients with mild cognitive impairment and Alzheimer’s disease. BMC Neurol. 15, 1–5. DOI: 10.1186/s12883–015–0268–6.
47. Santos Cláudia Y. et al. “Change in retinal structural anatomy during the preclinical stage of Alzheimer's disease.” Alzheimer's & Dementia (Amsterdam, Netherlands) Vol. 10 196–209. 7 Feb. 2018, DOI: 10.1016/j.dadm.2018.01.003.
48. Martins R. N. et al. Alzheimer's Disease: A Journey from Amyloid Peptides and Oxidative Stress, to Biomarker Technologies and Disease Prevention Strategies-Gains from AIBL and DIAN Cohort Studies.” Journal of Alzheimer's Disease: JAD Vol. 62, 3 (2018): 965–992. DOI: 10.3233/JAD-171145.
49. Colligris P. et al. Ocular Manifestations of Alzheimer's and Other Neurodegenerative Diseases: The Prospect of the Eye as a Tool for the Early Diagnosis of Alzheimer's Disease. Journal of Ophthalmology Vol. 2018 8538573. 30 Jul. 2018, DOI: 10.1155/2018/8538573.
50. Sánchez D. et al. Usefulness of peripapillary nerve fiber layer thickness assessed by optical coherence tomography as a biomarker for Alzheimer's disease. Scientific Reports Vol. 8, 1 16345. 5 Nov. 2018, DOI: 10.1038/s41598–018–34577–3.
51. Yoon S. P. et al. Retinal Microvascular and Neurodegenerative Changes in Alzheimer's Disease and Mild Cognitive Impairment Compared with Control Participants. Ophthalmology. Retina Vol. 3, 6 (2019): 489–499. DOI: 10.1016/j.oret.2019.02.002.
52. Yoon S. P. et al. Correlation of OCTA and Volumetric MRI in Mild Cognitive Impairment and Alzheimer's Disease. Ophthalmic Surgery, Lasers & Imaging Retina Vol. 50, 11 (2019): 709–718. DOI: 10.3928/23258160–20191031–06.
53. Querques G. et al. Functional and morphological changes of the retinal vessels in Alzheimer's disease and mild cognitive impairment. Scientific Reports Vol. 9, 1 63. 11 Jan. 2019, DOI: 10.1038/s41598–018–37271–6.
54. Shi H. et al. Identification of early pericyte loss and vascular amyloidosis in Alzheimer's disease retina. Acta Neuropathologica Vol. 139, 5 (2020): 813–836. DOI: 10.1007/s00401–020–02134-w.
55. Berisha F. et al. Retinal abnormalities in early Alzheimer's disease. Investigative Ophthalmology & Visual Science Vol. 48, 5 (2007): 2285–9. DOI: 10.1167/iovs.06–1029.
56. Feke G. T. et al. Retinal blood flow in mild cognitive impairment and Alzheimer's disease. Alzheimer's & Dementia (Amsterdam, Netherlands) vol. 1, 2 144–51. 23 Apr. 2015, DOI: 10.1016/j.dadm.2015.01.004.
57. Williams M. A. et al. Retinal microvascular network attenuation in Alzheimer's disease. Alzheimer's & Dementia (Amsterdam, Netherlands) vol. 1, 2 229–235. 16 May. 2015, DOI: 10.1016/j.dadm.2015.04.001.
58. Erichev V. P., Panyushkina L. A. Diagnostic value of functional and morphometric parameters of retina and optic nerve in patients with Alzheimer's disease. National Journal of Glaucoma. 2014; 13 (2): 5–10.
59. Erichev V. P., Panyushkina L. A., Tumanov V. P. Glaucoma and Alzheimer's disease: functional-structural and morphological features. X Congress of ophthalmologists of Russia. Collection of scientific materials. Moscow, June 17–19, 2015.
60. Kilivaeva G. A., Lobzin V. Yu., Emelin A. Yu., Maltsev D. S. Optic coherent tomography of retina in Alzheimer’s disease. Bulletin of the Russian Military Medical Academy. 2018; 20 (3S): 141–141.
61. Makhnovich EV. Abstract: Interrelation of cognitive disorders and changes in retinal neuroarchitectonics. Ph D. thesis – Moscow: 2019; 23 p.
62. Gulieva R. N. Retinal changes in Alzheimer's disease. Bulletin of Ophthalmology. 2020; 136 (3): 74–78. DOI: 10.17116/oftalma202013603174.
Review
For citations:
Lobzin V.Yu., Maltsev D.S., Strumentova E.S., Burnasheva M.A., Cheremisin S.S. Ophthalmological markers of Alzheimer's disease. Medical alphabet. 2022;(1):47-53. (In Russ.) https://doi.org/10.33667/2078-5631-2022-1-47-53
Views:
478
Email this article 