Skip to main content

Advertisement

SpringerLink
Log in

Beta-Amyloid Precursor Protein (βAPP) Processing in Alzheimer’s Disease (AD) and Age-Related Macular Degeneration (AMD)

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Amyloid is a generic term for insoluble, often intensely hydrophobic, fibrous protein aggregates that arise from inappropriately folded versions of naturally-occurring polypeptides. The abnormal generation and accumulation of amyloid, often referred to as amyloidogenesis, has been associated with the immune and pro-inflammatory pathology of several progressive age-related diseases of the human central nervous system (CNS) including Alzheimer’s disease (AD) and age-related macular degeneration (AMD). This ‘research perspective’ paper reviews some of the research history, biophysics, molecular-genetics and environmental factors concerning the contribution of amyloid beta (Aβ) peptides, derived from beta-amyloid precursor protein (βAPP), to AD and AMD that suggests an extensive similarity in immune and inflammatory degenerative mechanisms between these two CNS diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Selkoe DJ (1998) The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer’s disease. Trends Cell Biol 8:447–453

    Article  CAS  PubMed  Google Scholar 

  2. Jellinger KA (2012) Interaction between pathogenic proteins in neurodegenerative disorders. J Cell Mol Med 16:1166–1183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Yang X, Sun GY, Eckert GP, Lee JC (2014) Cellular membrane fluidity in amyloid precursor protein processing. Mol Neurobiol. doi:10.1007/s12035-014-8652-6

  4. Lukiw WJ (2013) Alzheimer’s disease (AD) as a disorder of the plasma membrane. Front Physiol 4:24. doi:10.3389/fphys.2013.00024

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Dorey E, Chang N, Liu QY, Yang Z, Zhang W (2014) Apolipoprotein E, amyloid-beta, and neuroinflammation in Alzheimer’s disease. Neurosci Bull 30:317–330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Glenner GG, Henry JH, Fujihara S (1981) Congophilic angiopathy in the pathogenesis of Alzheimer’s degeneration. Ann Pathol 1:120–129

    CAS  PubMed  Google Scholar 

  7. Glenner GG, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 425:534–539

    Article  CAS  Google Scholar 

  8. Glenner GG, Murphy MA (1989) Amyloidosis of the nervous system. J Neurol Sci 94:1–28

    Article  CAS  PubMed  Google Scholar 

  9. Buda O, Arsene D, Ceausu M, Dermengiu D, Curca GC (2009) Georges Marinesco and the early research in neuropathology. Neurology 72:88–91

    Article  CAS  PubMed  Google Scholar 

  10. Alzheimer A, Stelzmann RA, Schnitzlein HN, Murtagh FR (1995) An English translation of Alzheimer’s 1907 paper, “Uber eine eigenartige Erkankung der Hirnrinde”. Clin Anat 8:429–431

    Article  CAS  PubMed  Google Scholar 

  11. Armstrong RA (2008) Spatial correlations between beta-amyloid (Abeta) deposits and blood vessels in familial Alzheimer’s disease. Folia Neuropathol 46:241–248

    CAS  PubMed  Google Scholar 

  12. Furumoto S, Okamura N, Iwata R, Yanai K, Arai H, Kudo Y (2007) Recent advances in the development of amyloid imaging agents. Curr Top Med Chem 7:1773–1789

    Article  CAS  PubMed  Google Scholar 

  13. Mathis CA, Mason NS, Lopresti BJ, Klunk WE (2012) Development of positron emission tomography β-amyloid plaque imaging agents. Semin Nucl Med 42:423–432

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lengyel I, Tufail A, Hosaini HA, Luthert P, Bird AC, Jeffery G (2004) Association of drusen deposition with choroidal intercapillary pillars in the aging human eye. Invest Ophthalmol Vis Sci 45:2886–2892

    Article  PubMed  Google Scholar 

  15. Buschini E, Piras A, Nuzzi R, Vercelli A (2011) Age related macular degeneration and drusen: neuroinflammation in the retina. Prog Neurobiol 95:14–25

    Article  CAS  PubMed  Google Scholar 

  16. Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 12:383–388

    Article  CAS  PubMed  Google Scholar 

  17. Nalivaeva NN, Turner AJ (2013) The amyloid precursor protein: a biochemical enigma in brain development, function and disease. FEBS Lett 587:2046–2054

    Article  CAS  PubMed  Google Scholar 

  18. Sorrentino P, Iuliano A, Polverino A, Jacini F, Sorrentino G (2014) The dark sides of amyloid in Alzheimer’s disease pathogenesis. FEBS Lett 588:641–652

    Article  CAS  PubMed  Google Scholar 

  19. Ohno-Matsui K (2011) Parallel findings in age-related macular degeneration and Alzheimer’s disease. Prog Retin Eye Res 30:217–238

    Article  PubMed  Google Scholar 

  20. Huang EJ, Wu SH, Lai CH, Kuo CN, Wu PL, Chen CL, Chen CY, King YC, Wu PC (2014) Prevalence and risk factors for age-related macular degeneration in the elderly Chinese population in south-western Taiwan: the Puzih eye study. Eye (Lond). doi:10.1038/eye.2014.55

  21. Moon BG, Joe SG, Hwang JU, Kim HK, Choe J, Yoon YH (2012) Prevalence and risk factors of early-stage age-related macular degeneration in patients examined at a health promotion center in Korea. J Korean Med Sci 27:537–541

    Article  PubMed  PubMed Central  Google Scholar 

  22. Tharp WG, Sarkar IN (2013) Origins of amyloid-β. BMC Genomics 14:290. doi:10.1186/1471-2164-14-290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chen Y, Tang BL (2006) The amyloid precursor protein and postnatal neurogenesis/neuroregeneration. Biochem Biophys Res Commun 341:1–5

    Article  CAS  PubMed  Google Scholar 

  24. Chow VW, Mattson MP, Wong PC, Gleichmann M (2010) An overview of APP processing enzymes and products. Neuromol Med 12:1–12

    Article  CAS  Google Scholar 

  25. Exley C (2005) The aluminum-amyloid cascade hypothesis of Alzheimer’s disease. Subcell Biochem 38:225–234

    Article  CAS  PubMed  Google Scholar 

  26. Walton JR (2013) Aluminum involvement in the progression of Alzheimer’s disease. J Alzheimers Dis 35:7–43

    CAS  PubMed  Google Scholar 

  27. Kruck TP, Cui JG, Percy ME, Lukiw WJ (2004) Molecular shuttle chelation: the use of ascorbate, desferrioxamine and Feralex-G in combination to remove nuclear bound aluminum. Cell Mol Neurobiol 24:443–459

    Article  CAS  PubMed  Google Scholar 

  28. Crapper McLachlan DR, Dalton AJ, Kruck TP, Bell MY, Smith WL, Kalow W, Andrews DF (1991) Intramuscular desferrioxamine in patients with Alzheimer’s disease. Lancet 337:1304–1308

    Article  CAS  PubMed  Google Scholar 

  29. Percy ME, Kruck TP, Pogue AI, Lukiw WJ (2011) Towards the prevention of potential aluminum toxic effects and an effective treatment for Alzheimer’s disease. J Inorg Biochem 105:1505–1512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bhattacharjee S, Zhao Y, Hill JM, Percy ME, Lukiw WJ (2014) Aluminum and its potential contribution to Alzheimer’s disease (AD). Front Aging Neurosci 6:62. doi:10.3389/fnagi.2014.00062.eCollection 2014

    PubMed  PubMed Central  Google Scholar 

  31. Alexandrov PN, Zhao Y, Jones BM, Bhattacharjee S, Lukiw WJ (2013) Expression of the phagocytosis-essential protein TREM2 is down-regulated by an aluminum-induced miRNA-34a. J Inorg Biochem 128:267–269

    Article  CAS  PubMed  Google Scholar 

  32. Johnson LV, Leitner WP, Rivest AJ, Staples MK, Radeke MJ, Anderson DH (2002) 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 U S A 99:11830–11835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Luibl V, Isas JM, Kayed R, Glabe CG, Langen R, Chen J (2006) Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers. J Clin Invest 116:378–385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Dentchev T, Milam AH, Lee VM, Trojanowski JQ, Dunaief JL (2003) Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drusen from normal retinas. Mol Vis 9:184–190

    CAS  PubMed  Google Scholar 

  35. Anderson DH, Talaga KC, Rivest AJ, Barron E, Hageman GS, Johnson LV (2004) Characterization of beta amyloid assemblies in drusen: the deposits associated with aging and age-related macular degeneration. Exp Eye Res 78:243–256

    Article  CAS  PubMed  Google Scholar 

  36. Prakasam A, Muthuswamy A, Ablonczy Z, Greig NH, Fauq A, Rao KJ, Pappolla MA, Sambamurti K (2010) Differential accumulation of secreted AbetaPP metabolites in ocular fluids. J Alzheimers Dis 20:1243–1253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Aruoma OI, Jen SS, Watts HR, George J, Gentleman SM, Anderson PJ, Jen LS (2009) Acute and chronic effects of intravitreally injected beta-amyloid on the neurotransmitter system in the retina. Toxicology 256:92–100

    Article  CAS  PubMed  Google Scholar 

  38. Sieber MW, Jaenisch N, Brehm M, Guenther M, Linnartz-Gerlach B, Neumann H (2013) Attenuated inflammatory response in triggering receptor expressed on myeloid cells 2 (TREM2) knock-out mice following stroke. PLoS ONE 8(1):e52982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zhao Y, Bhattacharjee S, Jones BM, Dua P, Alexandrov PN, Hill JM, Lukiw WJ (2013) Regulation of TREM2 expression by an NF-кB-sensitive miRNA-34a. Neuroreport 24:318–323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Forabosco P, Ramasamy A, Trabzuni D, Walker R, Smith C, Bras J et al (2013) Insights into TREM2 biology by network analysis of human brain gene expression data. Neurobiol Aging 34:2699–2714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hickman SE, El Khoury J (2014) TREM2 and the neuro-immunology of Alzheimer’s disease. Biochem Pharmacol 88:495–498

    Article  CAS  PubMed  Google Scholar 

  42. Yin RH, Yu JT, Tan L (2014) The role of SORL1 in Alzheimer’s disease. Mol Neurobiol. doi:10.1007/s12035-014-8742-5. PubMed PMID: 24833601

  43. Cui JG, Hill JM, Zhao Y, Lukiw WJ (2007) Expression of inflammatory genes in the primary visual cortex of late-stage Alzheimer’s disease. Neuroreport 18:115–119

    Article  CAS  PubMed  Google Scholar 

  44. Waring SC, Rosenberg RN (2008) Genome-wide association studies in Alzheimer disease. Arch Neurol 65:329–334

    Article  PubMed  Google Scholar 

  45. Neumann H, Daly MJ (2013) Variant TREM2 as risk factor for Alzheimer’s disease. N Engl J Med 368:182–184

    Article  CAS  PubMed  Google Scholar 

  46. Alexandrov PN, Pogue A, Bhattacharjee S, Lukiw WJ (2011) Retinal amyloid peptides and complement factor H in transgenic models of Alzheimer’s disease. Neuroreport 22:623–627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zhao Y, Lukiw WJ (2013) TREM2 signaling, miRNA-34a and the extinction of phagocytosis. Front Cell Neurosci 7:131–135

    PubMed  PubMed Central  Google Scholar 

  48. Hickman SE, El Khoury J (2013) TREM2 and the neuroimmunology of Alzheimer’s disease. Biochem Pharmacol 88:495–498

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Jones BM, Bhattacharjee S, Dua P, Hill JM, Zhao Y, Lukiw WJ (2014) Regulating amyloidogenesis through the natural triggering receptor expressed inmyeloid/microglial cells 2 (TREM2). Front Cell Neurosci 8:94

    PubMed  PubMed Central  Google Scholar 

  50. Jiang T, Yu JT, Zhu XC, Tan L (2013) TREM2 in Alzheimer’s disease. Mol Neurobiol 48:180–185

    Article  CAS  PubMed  Google Scholar 

  51. Dawkins E, Small DH (2014) Insights into the physiological function of the β-amyloid precursor protein: beyond Alzheimer’s disease. J Neurochem 129:756–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Lukiw WJ (2013) Antagonism of NF-κB-up-regulated micro RNAs (miRNAs) in sporadic Alzheimer’s disease (AD): anti-NF-κB vs. anti-miRNA strategies. Front Genet 4:77–79

    PubMed  PubMed Central  Google Scholar 

  53. Lukiw WJ (2013) Variability in micro RNA (miRNA) abundance, speciation and complexity amongst different human populations and potential relevance to Alzheimer’s disease (AD). Front Cell Neurosci 7:133

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Lukiw WJ (2012) Amyloid beta (Aβ) peptide modulators and other current treatment strategies for Alzheimer’s disease (AD). Expert Opin Emerg Drugs. doi:10.1517/14728214.2012.672559. PubMed Central PMCID: PMC3399957

  55. Priller C, Bauer T, Mitteregger G, Krebs B, Kretzschmar HA, Herms J (2006) Synapse formation and function is modulated by the amyloid precursor protein. J Neurosci 26:7212–7221

    Article  CAS  PubMed  Google Scholar 

  56. Tyan SH, Shih AY, Walsh JJ, Maruyama H, Sarsoza F, Ku L, Eggert S, Hof PR, Koo EH, Dickstein DL (2012) Amyloid precursor protein (APP) regulates synaptic structure and function. Mol Cell Neurosci 51:43–52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hoe HS, Lee HK, Pak DT (2012) The upside of APP at synapses. CNS Neurosci Ther 18:47–56

    Article  CAS  PubMed  Google Scholar 

  58. Turner PR, O’Connor K, Tate WP, Abraham WC (2003) Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog Neurobiol 70:1–32

    Article  CAS  PubMed  Google Scholar 

  59. Barnham KJ, McKinstry WJ, Multhaup G, Galatis D, Morton CJ, Curtain CC, Williamson NA, White AR, Hinds MG, Norton RS, Beyreuther K, Masters CL, ParkerMW CR (2003) Structure of the Alzheimer’s disease amyloid precursor protein copper binding domain. A regulator of neuronal copper homeostasis. J Biol Chem 278:17401–17407

    Article  CAS  PubMed  Google Scholar 

  60. Duce JA, Tsatsanis A, Cater MA, James SA, Robb E, Wikhe K, Leong SL, Perez K, Johanssen T, Greenough MA, Cho HH, Galatis D, Moir RD, Masters CL, McLean C, Tanzi RE, Cappai R, Barnham KJ, Ciccotosto GD, Rogers JT, Bush AI (2010) Iron-export ferroxidase activity of β-amyloid precursor protein is inhibited by zinc in Alzheimer’s disease. Cell 142:857–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Porayette P, Gallego MJ, Kaltcheva MM, Meethal SV, Atwood CS (2007) Amyloid-beta precursor protein expression and modulation in human embryonic stem cells: a novel role for human chorionic gonadotropin. Biochem Biophys Res Commun 364:522–527

    Article  CAS  PubMed  Google Scholar 

  62. Sheng B, Song B, Zheng Z, Zhou F, Lu G, Zhao N, Zhang X, Gong Y (2009) Abnormal cleavage of APP impairs its functions in cell adhesion and migration. Neurosci Lett 450:327–331

    Article  CAS  PubMed  Google Scholar 

  63. Wang Z, Yang L, Zheng H (2012) Role of APP and Aβ in synaptic physiology. Curr Alzheimer Res 9:217–226

    Article  CAS  PubMed  Google Scholar 

  64. Allsop D, Ikeda S, Glenner GG (1989) Evidence for the derivation of a peptide ligand from the amyloid beta-protein precursor of Alzheimer’s disease. Prog Clin Biol Res 317:893–902

    CAS  PubMed  Google Scholar 

  65. Mattson MP (1997) Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol Rev 77:1081–1132

    CAS  PubMed  Google Scholar 

  66. Satpute-Krishnan P, Degiorgis JA, Conley MP, Jang M, Bearer EL (2006) A peptide zipcode sufficient for anterograde transport within amyloid precursor protein. Proc Natl Acad Sci 103:16532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Swomley AM, Förster S, Keeney JT, Triplett J, Zhang Z, Sultana R, Butterfield DA (2013) Abeta, oxidative stress in Alzheimer disease: evidence based on proteomics studies. Biochim Biophys Acta 1842:1248–1257

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Rossjohn J, Cappai R, Feil SC, Henry A, McKinstry WJ, Galatis D, Hesse L, Multhaup G, Beyreuther K, Masters CL, Parker MW (1999) Crystal structure of theN-terminal, growth factor-like domain of Alzheimer amyloid precursor protein. Nat Struct Biol 6:327–331

    Article  CAS  PubMed  Google Scholar 

  69. Goldstein LS (2001) Kinesin molecular motors: transport pathways, receptors, and human disease. Proc Natl Acad Sci U S A 98:6999–7003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Taru H, Suzuki T (2009) Regulation of the physiological function and metabolism of AbetaPP by AbetaPP binding proteins. J Alzheimers Dis 18:253–265

    Article  CAS  PubMed  Google Scholar 

  71. Ghavami S, Shojaei S, Yeganeh B, Ande SR, Jangamreddy JR, Mehrpour M, Christoffersson J, Chaabane W, Moghadam AR, Kashani HH, Hashemi M, Owji AA, Łos MJ (2014) Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog Neurobiol 112:24–49

    Article  CAS  PubMed  Google Scholar 

  72. Müller T, Schrötter A, Loosse C, Pfeiffer K, Theiss C, Kauth M, Meyer HE, Marcus K (2013) A ternary complex consisting of AICD, FE65, and TIP60 down-regulates stathmin1. Biochim Biophys Acta 1834:387–394

    Article  PubMed  CAS  Google Scholar 

  73. Li YY, Cui JG, Dua P, Pogue AI, Bhattacharjee S, Lukiw WJ (2011) Differential expression of miRNA-146a-regulated inflammatory genes in human primary neural, astroglial and microglial cells. Neurosci Lett 499:109–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lukiw WJ (2012) NF-кB-regulated micro RNAs (miRNAs) in primary human brain cells. Exp Neurol 235:484–490

    Article  CAS  PubMed  Google Scholar 

  75. Cui JG, Fraser PE, St George-Hyslop P, Westaway D, Lukiw WJ (2004) Potential roles for presenilin-1 in oxygen sensing and in glial-specific gene expression. Neuroreport 15:2025–2028

    Article  CAS  PubMed  Google Scholar 

  76. Zhao Y, Calon F, Julien C, Winkler JW, Petasis NA, Lukiw WJ, Bazan NG (2011) Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase- and PPARγ-mediated mechanisms in Alzheimer’s disease models. PLoS ONE 6:e15816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Skerka C, Chen Q, Fremeaux-Bacchi V, Roumenina LT (2013) Complement factor H related proteins (CFHRs). Mol Immunol 56:170–180

    Article  CAS  PubMed  Google Scholar 

  78. Fritsche LG, Fariss RN, Stambolian D, Abecasis GR, Curcio CA, Swaroop A (2014) Age-related macular degeneration: genetics and biology coming together. Annu Rev Genomics Hum Genet. doi:10.1146/annurev-genom-090413-025610. PubMed PMID: 24773320

  79. Zetterberg M, Landgren S, Andersson ME, Palmér MS, Gustafson DR, Skoog I, Minthon L, Thelle DS, Wallin A, Bogdanovic N, Andreasen N, Blennow K, Zetterberg H (2008) Association of complement factor H Y402H gene polymorphism with Alzheimer’s disease. Am J Med Genet B Neuropsychiatr Genet 147:720–726

    Article  CAS  Google Scholar 

  80. Le Fur I, Laumet G, Richard F, Fievet N, Berr C, Rouaud O, Delcourt C, Amouyel P, Lambert JC (2010) Association study of the CFH Y402H polymorphism with Alzheimer’s disease. Neurobiol Aging 31:165–166

    Article  PubMed  CAS  Google Scholar 

  81. Proitsi P, Lupton MK, Dudbridge F, Tsolaki M, Hamilton G, Daniilidou M, Pritchard M, Lord K, Martin BM, Johnson J, Craig D, Todd S, McGuinness B, Hollingworth P, Harold D, Kloszewska I, Soininen H, Mecocci P, Velas B, Gill M, Lawlor B, Rubinsztein DC, Brayne C, Passmore PA, Williams J, Lovestone S, Powell JF (2012) Alzheimer’s disease and age-related macular degeneration have different genetic models for complement gene variation. Neurobiol Aging 33:1843.e9–1843.e17. doi:10.1016/j.neurobiolaging.2011.12.036

    Article  CAS  Google Scholar 

  82. Liu MM, Chan CC, Tuo J (2012) Genetic mechanisms and age-related macular degeneration: common variants, rare variants, copy number variations, epigenetics, and mitochondrial genetics. Hum Genomics 6:13. doi:10.1186/1479-7364-6-13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Lukiw WJ, Zhao Y, Cui JG (2008) An NF-kB-sensitive micro RNA-146a-mediated inflammatory circuit in Alzheimer disease and in stressed human brain cells. J Biol Chem 283:31315–31322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Lukiw WJ, Alexandrov PN (2012) Regulation of complement factor H (CFH) by multiple miRNAs in Alzheimer’s disease (AD) brain. Mol Neurobiol 46:11–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Ambros V (2001) microRNAs: tiny regulators with great potential. Cell 107:823–826

    Article  CAS  PubMed  Google Scholar 

  86. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (2001) Identification of novel genes coding for small expressed RNAs. Science 294:853–858

    Article  CAS  PubMed  Google Scholar 

  87. Alexandrov PN, Dua P, Hill JM, Bhattacharjee S, Zhao Y, Lukiw WJ (2012) microRNA (miRNA) speciation in Alzheimer’s disease (AD) cerebrospinal fluid (CSF) and extracellular fluid (ECF). Int J Biochem Mol Biol 3:365–373

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Guo H, Ingolia NT, Weissman JS, Bartel DP (2010) Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466:835–840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Lukiw WJ, Surjyadipta B, Dua P, Alexandrov PN (2012) Common micro RNAs (miRNAs) target complement factor H (CFH) regulation in Alzheimer’s disease (AD) and in age-related macular degeneration (AMD). Int J Biochem Mol Biol 3:105–116

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Anderson DH, Radeke MJ, Gallo NB, Chapin EA, Johnson PT, Curletti CR, Hancox LS, Hu J, Ebright JN, Malek G, Hauser MA, Rickman CB, Bok D, Hageman GS, Johnson LV (2010) The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited. Prog Retin Eye Res 29:95–112

    Article  CAS  PubMed  Google Scholar 

  91. Quan YL, Zhou AY, Feng ZH (2012) Association between complementary factor H Y402H polymorphisms and age-related macular degeneration in Chinese: systematic review and meta-analysis. Int J Ophthalmol 5:242–246

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Kondo N, Bessho H, Honda S, Negi A (2011) Complement factor H Y402H variant and risk of age-related macular degeneration in Asians: a systematic review and meta-analysis. Ophthalmology 118:339–344

    Article  PubMed  Google Scholar 

  93. Ermilov VV, Tiurenkov IN, Nesterova AA, Zagrebin VA (2013) Alzheimer’s disease and geriatric eye diseases in the aspect of amyloid genesis. Arkh Patol 75:37–42

    CAS  PubMed  Google Scholar 

  94. Frost S, Kanagasingam Y, Sohrabi H, Vignarajan J, Bourgeat P, Salvado O, Villemagne V, Rowe CC, Macaulay SL, Szoeke C, Ellis KA, Ames D, Masters CL, Rainey-Smith S, Martins RN, Group AR (2013) Retinal vascular biomarkers for early detection and monitoring of Alzheimer’s disease. Transl Psychiatry 3:e233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Crabb JW, Miyagi M, Gu X, Shadrach K, West KA, Sakaguchi H, Kamei M, Hasan A, Yan L, Rayborn ME, Salomon RG, Hollyfield JG (2002) Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc Natl Acad Sci U S A 99:14682–14687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Jiang T, Yu JT, Zhu XC, Tan MS, Gu LZ, Zhang YD et al (2014) Triggering receptor expressed on myeloid cells 2 knockdown exacerbates aging-related neuroinflammation and cognitive deficiency in senescence-accelerated mouse prone 8 mice. Neurobiol Aging 35:1243–1251

    Article  CAS  PubMed  Google Scholar 

  97. Cai J, Qi X, Kociok N, Skosyrski S, Emilio A, Ruan Q, Han S, Liu L, Chen Z, Bowes Rickman C, Golde T, Grant MB, Saftig P, Serneels L, de Strooper B, Joussen AM, Boulton ME (2012) beta-Secretase (BACE1) inhibition causes retinal pathology by vascular dysregulation and accumulation of age pigment. EMBO Mol Med 4:980–991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318

    Article  CAS  PubMed  Google Scholar 

  99. Griciuc A, Serrano-Pozo A, Parrado AR, Lesinski AN, Asselin CN, Mullin K, Hooli B, Choi SH, Hyman BT, Tanzi RE (2013) Alzheimer’s disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron 78:631–643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Sivak JM (2013) The aging eye: common degenerative mechanisms between the Alzheimer’s brain and retinal disease. Invest Ophthalmol Vis Sci 54:871–880

    Article  PubMed  CAS  Google Scholar 

  101. Baker ML, Wang JJ, Rogers S, Klein R, Kuller LH, Larsen EK, Wong TY (2009) Early age-related macular degeneration, cognitive function, and dementia: the Cardiovascular Health Study. Arch Ophthalmol 127:667–673

    Article  PubMed  PubMed Central  Google Scholar 

  102. Woo SJ, Park KH, Ahn J, Choe JY, Jeong H, Han JW, Kim TH, Kim KW (2012) Cognitive impairment in age-related macular degeneration and geographic atrophy. Ophthalmology 119:2094–2101

    Article  PubMed  Google Scholar 

  103. Raj A, Rifkin SA, Andersen E, van Oudenaarden A (2010) Variability in gene expression underlies incomplete penetrance. Nature 463:913–918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Chiu K, Chan TF, Wu A, Leung IY, So KF, Chang RC (2012) Neurodegeneration of the retina in mouse models of Alzheimer’s disease: what can we learn from the retina? Age (Dordr) 34:633–649

    Article  CAS  Google Scholar 

  105. Logue MW, Schu M, Vardarajan BN, Farrell J, Lunetta KL, Jun G, Baldwin CT, Deangelis MM, Farrer LA (2014) A search for age-related macular degeneration risk variants in Alzheimer disease genes and pathways. Neurobiol Aging 35:1510.e7–1510.e18

    Article  CAS  Google Scholar 

  106. Olson MV (2012) Human genetic individuality. Annu Rev Genomics Hum Genet 13:1–27

    Article  CAS  PubMed  Google Scholar 

  107. Ding JD, Lin J, Mace BE, Herrmann R, Sullivan P, Bowes Rickman C (2008) Targeting age-related macular degeneration with Alzheimer’s disease based immunotherapies: anti-amyloid-beta antibody attenuates pathologies in an age-related macular degeneration mouse model. Vis Res 48:339–345

    Article  CAS  PubMed  Google Scholar 

  108. Ding JD, Johnson LV, Herrmann R, Farsiu S, Smith SG, Groelle M, Mace BE, Sullivan P, Jamison JA, Kelly U, Harrabi O, Bollini SS, Dilley J, Kobayashi D, Kuang B, Li W, Pons J, Lin JC, Bowes Rickman C (2011) Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration. Proc Natl Acad Sci U S A 108:E279–E287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Hu N, Tan MS, Sun L, Jiang T, Wang YL, Tan L, Zhang W, Yu JT, Tan L (2014) Decreased expression of CD33 in peripheral mononuclear cells of Alzheimer’s disease patients. Neurosci Lett 563:51–54

    Article  CAS  PubMed  Google Scholar 

  110. Dutescu RM, Li QX, Crowston J, Masters CL, Baird PN, Culvenor JG (2009) Amyloid precursor protein processing and retinal pathology in mouse models of Alzheimer’s disease. Graefes Arch Clin Exp Ophthalmol 247:1213–1221

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The work in this research perspective was presented in part at the Alzheimer Association International Conference 2013 (AAIC 2013) Annual Meeting held in Boston MA, USA and at the AAIC 2014 held in Copenhagen, Denmark. Sincere thanks are extended to Drs. PN Alexandrov, F Culicchia, C Eicken, and C Hebel for the short postmortem interval (PMI) human brain tissues or extracts, miRNA array work, and initial data interpretation and to D Guillot and J Lockwood for the expert technical assistance. Additional thanks are extended to the physicians and neuropathologists of Canada and the USA who have provided high-quality, short postmortem interval human brain and retinal tissues for study. Additional human control and AD brain tissues were provided by the Memory Impairments and Neurological Disorders (MIND) Institute and the University of California, Irvine Alzheimer’s Disease Research Center (UCI-ADRC; NIA P50 AG16573). Research on miRNA in the Lukiw laboratory involving the innate-immune response in AD, amyloidogenesis, and neuro-inflammation was supported through a COBRE III Pilot Project NIH/NIGMS Grant P30-GM103340, an unrestricted grant to the LSU Eye Center from Research to Prevent Blindness (RPB); the Louisiana Biotechnology Research Network (LBRN); and NIH grants NEI EY006311, NIA AG18031, and NIA AG038834. Research on AD, Down’s syndrome, and amyloidosis in the Sambamurti laboratory are supported by the Alzheimer’s Association IIRG 10-173180 and NIH NIA AG046200.

Author information

Authors and Affiliations

  1. LSU Neuroscience Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite 904, New Orleans, LA, 70112, USA

    Yuhai Zhao, Surjyadipta Bhattacharjee, Brandon M. Jones, James M. Hill & Walter J. Lukiw

  2. Department of Ophthalmology, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite 904, New Orleans, LA, 70112, USA

    James M. Hill & Walter J. Lukiw

  3. Department of Microbiology, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite 904, New Orleans, LA, 70112, USA

    James M. Hill

  4. Department of Pharmacology, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite 904, New Orleans, LA, 70112, USA

    James M. Hill

  5. Department of Neurology, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite 904, New Orleans, LA, 70112, USA

    James M. Hill & Walter J. Lukiw

  6. Department of Natural Sciences, Infectious Diseases, Experimental Therapeutics and Human Toxicology Lab, Southern University at New Orleans, New Orleans, LA, 70126, USA

    Christian Clement

  7. Medical University of South Carolina, Charleston, SC, 29425, USA

    Kumar Sambamurti

  8. Department of Health Information Management, Louisiana State University, Ruston, LA, 71272, USA

    Prerna Dua

Authors
  1. Yuhai Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Surjyadipta Bhattacharjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brandon M. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James M. Hill
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christian Clement
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kumar Sambamurti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Prerna Dua
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Walter J. Lukiw
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Walter J. Lukiw.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, Y., Bhattacharjee, S., Jones, B.M. et al. Beta-Amyloid Precursor Protein (βAPP) Processing in Alzheimer’s Disease (AD) and Age-Related Macular Degeneration (AMD). Mol Neurobiol 52, 533–544 (2015). https://doi.org/10.1007/s12035-014-8886-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-014-8886-3

Keywords

Search

Navigation