Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease

JCI Insight

Volumn 2, Issue 16, 2017, Pages

  Koronyo, Yosef ^a   Biggs, David ^b   Barron, Ernesto ^c   Boyer, David S ^d   Pearlman, Joel A ^e   Au, William J ^f   Kile, Shawn J ^f   Blanco, Austin ^b   Fuchs, Dieu Trang ^a   Ashfaq, Adeel ^g   Frautschy, Sally ^g,h,i   Cole, Gregory M ^g,h,i   Miller, Carol A ^j   Hinton, David R ^j   Verdooner, Steven R ^b   Black, Keith L ^a   Koronyo Hamaoui, Maya ^a  

^a CEDARS SINAI MEDICAL CENTER   (United States)

^b Neurovision Imaging LLC   (United States)

^c DOHENY EYE INSTITUTE   (United States)

^d RETINA VITREOUS ASSOCIATES MEDICAL GROUP   (United States)

^e Retinal Medical Group   (United States)

^f Sutter Medical Center   (United States)

^g UNIVERSITY OF CALIFORNIA   (United States)

^h GERIATRIC RESEARCH EDUCATION AND CLINICAL CENTER   (United States)

ⁱ VA GREATER LOS ANGELES HEALTHCARE SYSTEM   (United States)

^j UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85034004376     PISSN: None     EISSN: 23793708     Source Type: Journal    
DOI: 10.1172/JCI.INSIGHT.93621     Document Type: Article

References (113)

1. Alzheimer’s Association. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 2016;12 (4):459–509.
2. De Strooper B, Karran E. The cellular phase of Alzheimer’s disease. Cell. 2016;164(4):603–615.
3. Hardy J, Duff K, Hardy KG, Perez-Tur J, Hutton M. Genetic dissection of Alzheimer’s disease and related dementias: amyloid and its relationship to tau. Nat Neurosci. 1998;1 (5):355–358.
4. Bateman RJ, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012;367 (9):795–804.
5. Bilgel M, et al. Individual estimates of age at detectable amyloid onset for risk factor assessment. Alzheimers Dement. 2016;12 (4):373–379.
6. Perrin RJ, Fagan AM, Holtzman DM. Multimodal techniques for diagnosis and prognosis of Alzheimer’s disease. Nature. 2009;461 (7266):916–922.
7. Klunk WE, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol. 2004;55 (3):306–319.
8. Blennow K, Mattsson N, Schöll M, Hansson O, Zetterberg H. Amyloid biomarkers in Alzheimer’s disease. Trends Pharmacol Sci. 2015;36(5):297–309.
9. Khan TK, Alkon DL. Alzheimer’s disease cerebrospinal fluid and neuroimaging biomarkers: diagnostic accuracy and relationship to drug efficacy. J Alzheimers Dis. 2015;46 (4):817–836.
10. Tu P, Fu H, Cui M. Compounds for imaging amyloid-β deposits in an Alzheimer’s brain: a patent review. Expert Opin Ther Pat. 2015;25 (4):413–423.
11. Hart NJ, Koronyo Y, Black KL, Koronyo-Hamaoui M. Ocular indicators of Alzheimer’s: exploring disease in the retina. Acta Neuropathol. 2016;132 (6):767–787.
12. The Retina. In: Purves D, et al, eds. Neuroscience. 2nd ed. Chapters 11 and 12. Sunderland (MA): Sinauer Associates; 2001.
13. Byerly MS, Blackshaw S. Vertebrate retina and hypothalamus development. Wiley Interdiscip Rev Syst Biol Med. 2009;1 (3):380–389.
14. Trost A, et al. Brain and Retinal Pericytes: Origin, Function and Role. Front Cell Neurosci. 2016;10:20.
15. Bayhan HA, Aslan Bayhan S, Celikbilek A, Tanık N, Gürdal C. Evaluation of the chorioretinal thickness changes in Alzheimer’s disease using spectral-domain optical coherence tomography. Clin Experiment Ophthalmol. 2015;43 (2):145–151.
16. Blanks JC, Schmidt SY, Torigoe Y, Porrello KV, Hinton DR, Blanks RH. Retinal pathology in Alzheimer’s disease. II. Regional neuron loss and glial changes in GCL. Neurobiol Aging. 1996;17(3):385–395.
17. Coppola G, et al. Optical coherence tomography in Alzheimer’s disease: a meta-analysis. PLoS One. 2015;10(8):e0134750.
18. Curcio CA, Drucker DN. Retinal ganglion cells in Alzheimer’s disease and aging. Ann Neurol. 1993;33 (3):248–257.
19. Feke GT, Hyman BT, Stern RA, Pasquale LR. Retinal blood flow in mild cognitive impairment and Alzheimer’s disease. Alzheimers Dement (Amst). 2015;1 (2):144–151.
20. Frost S, et al. Retinal vascular biomarkers for early detection and monitoring of Alzheimer’s disease. Transl Psychiatry. 2013;3:e233.
21. Gao L, Liu Y, Li X, Bai Q, Liu P. Abnormal retinal nerve fiber layer thickness and macula lutea in patients with mild cognitive impairment and Alzheimer’s disease. Arch Gerontol Geriatr. 2015;60 (1):162–167.
22. Guo L, Duggan J, Cordeiro MF. Alzheimer’s disease and retinal neurodegeneration. Curr Alzheimer Res. 2010;7(1):3–14.
23. Hinton DR, Sadun AA, Blanks JC, Miller CA. Optic-nerve degeneration in Alzheimer’s disease. N Engl J Med. 1986;315 (8):485–487.
24. Kirbas S, Turkyilmaz K, Anlar O, Tufekci A, Durmus M. Retinal nerve fiber layer thickness in patients with Alzheimer disease. J Neuroophthalmol. 2013;33 (1):58–61.
25. Kromer R, Serbecic N, Hausner L, Froelich L, Aboul-Enein F, Beutelspacher SC. Detection of retinal nerve fiber layer defects in Alzheimer’s disease Using SD-OCT. Front Psychiatry. 2014;5:22.
26. La Morgia C, et al. Melanopsin retinal ganglion cell loss in Alzheimer disease. Ann Neurol. 2016;79 (1):90–109.
27. Marziani E, et al. Evaluation of retinal nerve fiber layer and ganglion cell layer thickness in Alzheimer’s disease using spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2013;54 (9):5953–5958.
28. Moreno-Ramos T, Benito-León J, Villarejo A, Bermejo-Pareja F. Retinal nerve fiber layer thinning in dementia associated with Parkinson’s disease, dementia with Lewy bodies, and Alzheimer’s disease. J Alzheimers Dis. 2013;34 (3):659–664.
29. Moschos MM, et al. Structural and functional impairment of the retina and optic nerve in Alzheimer’s disease. Curr Alzheimer Res. 2012;9 (7):782–788.
30. Paquet C, Boissonnot M, Roger F, Dighiero P, Gil R, Hugon J. Abnormal retinal thickness in patients with mild cognitive impairment and Alzheimer’s disease. Neurosci Lett. 2007;420(2):97–99.
31. Shi Z, et al. Greater attenuation of retinal nerve fiber layer thickness in Alzheimer’s disease patients. J Alzheimers Dis. 2014;40 (2):277–283.
32. Trick GL, Barris MC, Bickler-Bluth M. Abnormal pattern electroretinograms in patients with senile dementia of the Alzheimer type. Ann Neurol. 1989;26 (2):226–231.
33. Williams MA, et al. Retinal microvascular network attenuation in Alzheimer’s disease. Alzheimers Dement (Amst). 2015;1 (2):229–235.
34. Patton N, Aslam T, Macgillivray T, Pattie A, Deary IJ, Dhillon B. Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures. J Anat. 2005;206 (4):319–348.
35. Vecino E, Rodriguez FD, Ruzafa N, Pereiro X, Sharma SC. Glia-neuron interactions in the mammalian retina. Prog Retin Eye Res. 2016;51:1–40.
36. Morin PJ, et al. Amyloid precursor protein is synthesized by retinal ganglion cells, rapidly transported to the optic nerve plasma membrane and nerve terminals, and metabolized. J Neurochem. 1993;61 (2):464–473.
37. Cai J, et al. β-Secretase (BACE1) inhibition causes retinal pathology by vascular dysregulation and accumulation of age pigment. EMBO Mol Med. 2012;4 (9):980–991.
38. Li L, et al. BACE1 in the retina: a sensitive biomarker for monitoring early pathological changes in Alzheimer’s disease. Neural Regen Res. 2016;11 (3):447–453.
39. Alexandrov PN, Pogue A, Bhattacharjee S, Lukiw WJ. Retinal amyloid peptides and complement factor H in transgenic models of Alzheimer’s disease. Neuroreport. 2011;22 (12):623–627.
40. Koronyo-Hamaoui M, et al. Identification of amyloid plaques in retinas from Alzheimer’s patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. Neuroimage. 2011;54 Suppl 1:S204–S217.
41. Schön C, et al. Long-term in vivo imaging of fibrillar tau in the retina of P301S transgenic mice. PLoS ONE. 2012;7 (12):e53547.
42. Tsai Y, et al. Ocular changes in TgF344-AD rat model of Alzheimer’s disease. Invest Ophthalmol Vis Sci. 2014;55 (1):523–534.
43. Ho CY, Troncoso JC, Knox D, Stark W, Eberhart CG. Beta-amyloid, phospho-tau and alpha-synuclein deposits similar to those in the brain are not identified in the eyes of Alzheimer’s and Parkinson’s disease patients. Brain Pathol. 2014;24 (1):25–32.
44. Ju YE, et al. Sleep quality and preclinical Alzheimer disease. JAMA Neurol. 2013;70 (5):587–593.
45. Du LY, et al. Alzheimer’s disease-related protein expression in the retina of Octodon degus. PLoS ONE. 2015;10 (8):e0135499.
46. Dutescu RM, Li QX, Crowston J, Masters CL, Baird PN, Culvenor JG. Amyloid precursor protein processing and retinal pathology in mouse models of Alzheimer’s disease. Graefes Arch Clin Exp Ophthalmol. 2009;247 (9):1213–1221.
47. Edwards MM, Rodríguez JJ, Gutierrez-Lanza R, Yates J, Verkhratsky A, Lutty GA. Retinal macroglia changes in a triple transgenic mouse model of Alzheimer’s disease. Exp Eye Res. 2014;127:252–260.
48. Gao L, et al. Neuroprotective effect of memantine on the retinal ganglion cells of APPswe/PS1ΔE9 mice and its immunomodulatory mechanisms. Exp Eye Res. 2015;135:47–58.
49. Gupta VK, et al. Amyloid β accumulation and inner retinal degenerative changes in Alzheimer’s disease transgenic mouse. Neurosci Lett. 2016;623:52–56.
50. He Y, Zhao H, Su G. Ginsenoside Rg1 decreases neurofibrillary tangles accumulation in retina by regulating activities of neprilysin and PKA in retinal cells of AD mice model. J Mol Neurosci. 2014;52 (1):101–106.
51. Koronyo Y, Salumbides BC, Black KL, Koronyo-Hamaoui M. Alzheimer’s disease in the retina: imaging retinal aβ plaques for early diagnosis and therapy assessment. Neurodegener Dis. 2012;10 (1-4):285–293.
52. Liu B, et al. Amyloid-peptide vaccinations reduce {beta}-amyloid plaques but exacerbate vascular deposition and inflammation in the retina of Alzheimer’s transgenic mice. Am J Pathol. 2009;175 (5):2099–2110.
53. More SS, Vince R. Hyperspectral imaging signatures detect amyloidopathy in Alzheimer’s mouse retina well before onset of cognitive decline. ACS Chem Neurosci. 2015;6 (2):306–315.
54. Ning A, Cui J, To E, Ashe KH, Matsubara J. Amyloid-beta deposits lead to retinal degeneration in a mouse model of Alzheimer disease. Invest Ophthalmol Vis Sci. 2008;49 (11):5136–5143.
55. Park SW, et al. Intracellular amyloid beta alters the tight junction of retinal pigment epithelium in 5XFAD mice. Neurobiol Aging. 2014;35 (9):2013–2020.
56. Parthasarathy R, et al. Reduction of amyloid-beta levels in mouse eye tissues by intra-vitreally delivered neprilysin. Exp Eye Res. 2015;138:134–144.
57. Perez SE, Lumayag S, Kovacs B, Mufson EJ, Xu S. Beta-amyloid deposition and functional impairment in the retina of the APPswe/PS1DeltaE9 transgenic mouse model of Alzheimer’s disease. Invest Ophthalmol Vis Sci. 2009;50 (2):793–800.
58. Pogue AI, Dua P, Hill JM, Lukiw WJ. Progressive inflammatory pathology in the retina of aluminum-fed 5xFAD transgenic mice. J Inorg Biochem. 2015;152:206–209.
59. Williams PA, et al. Retinal ganglion cell dendritic degeneration in a mouse model of Alzheimer’s disease. Neurobiol Aging. 2013;34 (7):1799–1806.
60. Yang Y, et al. Suppressed retinal degeneration in aged wild type and APPswe/PS1ΔE9 mice by bone marrow transplantation. PLoS ONE. 2013;8 (6):e64246.
61. Zhao H, et al. Hyperphosphorylation of tau protein by calpain regulation in retina of Alzheimer’s disease transgenic mouse. Neurosci Lett. 2013;551:12–16.
62. Kobayashi S, et al. Quantitative analysis of brain perfusion SPECT in Alzheimer’s disease using a fully automated regional cerebral blood flow quantification software, 3DSRT. J Neurol Sci. 2008;264 (1-2):27–33.
63. Kumaraswamy P, Sethuraman S, Krishnan UM. Mechanistic insights of curcumin interactions with the core-recognition motif of β-amyloid peptide. J Agric Food Chem. 2013;61 (13):3278–3285.
64. Masuda Y, et al. Solid-state NMR analysis of interaction sites of curcumin and 42-residue amyloid β-protein fibrils. Bioorg Med Chem. 2011;19 (20):5967–5974.
65. Mutsuga M, et al. Binding of curcumin to senile plaques and cerebral amyloid angiopathy in the aged brain of various animals and to neurofibrillary tangles in Alzheimer’s brain. J Vet Med Sci. 2012;74 (1):51–57.
66. Yanagisawa D, et al. Relationship between the tautomeric structures of curcumin derivatives and their Abeta-binding activities in the context of therapies for Alzheimer’s disease. Biomaterials. 2010;31 (14):4179–4185.
67. Yanagisawa D, Taguchi H, Yamamoto A, Shirai N, Hirao K, Tooyama I. Curcuminoid binds to amyloid-β1-42 oligomer and fibril. J Alzheimers Dis. 2011;24 Suppl 2:33–42.
68. Ryu EK, Choe YS, Lee KH, Choi Y, Kim BT. Curcumin and dehydrozingerone derivatives: synthesis, radiolabeling, and evaluation for beta-amyloid plaque imaging. J Med Chem. 2006;49 (20):6111–6119.
69. Frautschy SA, Cole GM, Baird A. Phagocytosis and deposition of vascular beta-amyloid in rat brains injected with Alzheimer beta-amyloid. Am J Pathol. 1992;140 (6):1389–1399.
70. Ahmed M, et al. Structural conversion of neurotoxic amyloid-beta (1-42) oligomers to fibrils. Nat Struct Mol Biol. 2010;17 (5):561–567.
71. Walsh DM, et al. Amyloid beta-protein fibrillogenesis. Structure and biological activity of protofibrillar intermediates. J Biol Chem. 1999;274(36):25945–25952.
72. Lashuel HA, Hartley D, Petre BM, Walz T, Lansbury PT. Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature. 2002;418 (6895):291.
73. Teplow DB. On the subject of rigor in the study of amyloid β-protein assembly. Alzheimers Res Ther. 2013;5 (4):39.
74. Cox KH, Pipingas A, Scholey AB. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. J Psychopharmacol (Oxford). 2015;29 (5):642–651.
75. DiSilvestro RA, Joseph E, Zhao S, Bomser J. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J. 2012;11:79.
76. Berisha F, Feke GT, Trempe CL, McMeel JW, Schepens CL. Retinal abnormalities in early Alzheimer’s disease. Invest Ophthalmol Vis Sci. 2007;48(5):2285–2289.
77. Kesler A, Vakhapova V, Korczyn AD, Naftaliev E, Neudorfer M. Retinal thickness in patients with mild cognitive impairment and Alzheimer’s disease. Clin Neurol Neurosurg. 2011;113(7):523–526.
78. Lu Y, et al. Retinal nerve fiber layer structure abnormalities in early Alzheimer’s disease: evidence in optical coherence tomography. Neurosci Lett. 2010;480 (1):69–72.
79. Trick GL, Trick LR, Morris P, Wolf M. Visual field loss in senile dementia of the Alzheimer’s type. Neurology. 1995;45 (1):68–74.
80. Gilmore GC, Wenk HE, Naylor LA, Koss E. Motion perception and Alzheimer’s disease. J Gerontol. 1994;49(2):P52–P57.
81. Risacher SL, et al. Visual contrast sensitivity in Alzheimer’s disease, mild cognitive impairment, and older adults with cognitive complaints. Neurobiol Aging. 2013;34 (4):1133–1144.
82. Zuroff L, Daley D, Black KL, Koronyo-Hamaoui M. Clearance of cerebral Aβ in Alzheimer’s disease: reassessing the role of microglia and monocytes. Cell Mol Life Sci. 2017;74 (12):2167–2201.
83. Goldstein LE, et al. Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer’s disease. Lancet. 2003;361 (9365):1258–1265.
84. Bodis-Wollner I, Kozlowski PB, Glazman S, Miri S. α-synuclein in the inner retina in parkinson disease. Ann Neurol. 2014;75 (6):964–966.
85. Blanks JC, Hinton DR, Sadun AA, Miller CA. Retinal ganglion cell degeneration in Alzheimer’s disease. Brain Res. 1989;501(2):364–372.
86. Katz B, Rimmer S, Iragui V, Katzman R. Abnormal pattern electroretinogram in Alzheimer’s disease: evidence for retinal ganglion cell degeneration? Ann Neurol. 1989;26 (2):221–225.
87. Cordeiro MF, et al. Imaging multiple phases of neurodegeneration: a novel approach to assessing cell death in vivo. Cell Death Dis. 2010;1:e3.
88. Meli G, et al. Conformational targeting of intracellular Aβ oligomers demonstrates their pathological oligomerization inside the endoplasmic reticulum. Nat Commun. 2014;5:3867.
89. Pensalfini A, et al. Intracellular amyloid and the neuronal origin of Alzheimer neuritic plaques. Neurobiol Dis. 2014;71:53–61.
90. Armstrong RA. Beta-amyloid plaques: stages in life history or independent origin? Dement Geriatr Cogn Disord. 1998;9(4):227–238.
91. Vinters HV. Cerebral amyloid angiopathy. A critical review. Stroke. 1987;18(2):311–324.
92. Frost S, Martins RN, Kanagasingam Y. Ocular biomarkers for early detection of Alzheimer’s disease. J Alzheimers Dis. 2010;22 (1):1–16.
93. Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci. 2004;5 (5):347–360.
94. Ruitenberg A, et al. Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol. 2005;57 (6):789–794.
95. Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci. 2011;12 (12):723–738.
96. Kimbrough IF, Robel S, Roberson ED, Sontheimer H. Vascular amyloidosis impairs the gliovascular unit in a mouse model of Alzheimer’s disease. Brain. 2015;138 (Pt 12):3716–3733.
97. Yang F, et al. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005;280 (7):5892–5901.
98. Bieschke J, Zhang Q, Powers ET, Lerner RA, Kelly JW. Oxidative metabolites accelerate Alzheimer’s amyloidogenesis by a two-step mechanism, eliminating the requirement for nucleation. Biochemistry. 2005;44 (13):4977–4983.
99. Han M, et al. Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging. J Biomed Opt. 2007;12 (2):024012.
100. Schnell SA, Staines WA, Wessendorf MW. Reduction of lipofuscin-like autofluorescence in fluorescently labeled tissue. J Histochem Cytochem. 1999;47 (6):719–730.
101. Maiti P, et al. A comparative study of dietary curcumin, nanocurcumin, and other classical amyloid-binding dyes for labeling and imaging of amyloid plaques in brain tissue of 5×-familial Alzheimer’s disease mice. Histochem Cell Biol. 2016;146 (5):609–625.
102. Rao PP, Mohamed T, Teckwani K, Tin G. Curcumin binding to beta amyloid: a computational study. Chem Biol Drug Des. 2015;86 (4):813–820.
103. Garcia-Alloza M, Borrelli LA, Rozkalne A, Hyman BT, Bacskai BJ. Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. J Neurochem. 2007;102 (4):1095–1104.
104. Dhillon N, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008;14 (14):4491–4499.
105. Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J Agric Food Chem. 2010;58 (4):2095–2099.
106. Dadhaniya P, et al. Safety assessment of a solid lipid curcumin particle preparation: acute and subchronic toxicity studies. Food ChemToxicol. 2011;49 (8):1834–1842.
107. Kayabasi U, Sergott R, Rispoli M. Retinal examination for the diagnosis of Alzheimer’s disease. J Ophthalmic Pathol. 2014;3(4):1–4.
108. Dentchev T, Milam AH, Lee VM, Trojanowski JQ, Dunaief JL. Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drusen from normal retinas. Mol Vis. 2003;9:184–190.
109. Johnson LV, Leitner WP, Rivest AJ, Staples MK, Radeke MJ, Anderson DH. The Alzheimer’s A beta -peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. Proc Natl Acad Sci USA. 2002;99 (18):11830–11835.
110. Ratnayaka JA, Serpell LC, Lotery AJ. Dementia of the eye: the role of amyloid beta in retinal degeneration. Eye (Lond). 2015;29 (8):1013–1026.
111. Algvere PV, Kvanta A, Seregard S. Drusen maculopathy: a risk factor for visual deterioration. Acta Ophthalmol. 2016;94 (5):427–433.
112. Jack CR, et al. Brain β-amyloid load approaches a plateau. Neurology. 2013;80(10):890–896.
113. Begum AN, et al. Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer’s disease. J Pharmacol Exp Ther. 2008;326 (1):196–208.