Neuronal heparan sulfates promote amyloid pathology by modulating brain amyloid-β clearance and aggregation in Alzheimer's disease

Science Translational Medicine

Volumn 8, Issue 332, 2016, Pages

  Liu, Chia Chen ^a   Zhao, Na ^a   Yamaguchi, Yu ^b   Cirrito, John R ^c   Kanekiyo, Takahisa ^a   Holtzman, David M ^c   Bu, Guojun ^a,d  

^a MAYO GRADUATE SCHOOL   (United States)

^b BURNHAM INSTITUTE   (United States)

^c WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d XIAMEN UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; HEPARAN SULFATE; PROTEOHEPARAN SULFATE; AMYLOID;

ADULT; AGED; ALZHEIMER DISEASE; AMYLOID PLAQUE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN INTERSTITIAL FLUID; CLINICAL ARTICLE; CONTROLLED STUDY; EXT1 GENE; GENE; HIPPOCAMPUS; HUMAN; HUMAN TISSUE; MICRODIALYSIS; MOUSE; MOUSE MODEL; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; OLIGOMERIZATION; PRIORITY JOURNAL; PROTEIN AGGREGATION; TEMPORAL CORTEX; VASCULAR AMYLOIDOSIS; ANIMAL; DISEASE MODEL; INFLAMMATION; METABOLISM; NERVE CELL; PATHOLOGY; PROTEINOSIS; VASCULARIZATION; VERY ELDERLY;

AGED, 80 AND OVER; ALZHEIMER DISEASE; AMYLOID; AMYLOID BETA-PEPTIDES; ANIMALS; DISEASE MODELS, ANIMAL; HEPARITIN SULFATE; HIPPOCAMPUS; HUMANS; INFLAMMATION; MICE; NEURONS; PROTEIN AGGREGATION, PATHOLOGICAL;

EID: 84962639341     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aad3650     Document Type: Article

References (80)

1. J. Hardy, D. J. Selkoe, The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 297, 353-356 (2002).
2. D. J. Selkoe, Deciphering the genesis and fate of amyloid β-protein yields novel therapies for Alzheimer disease. J. Clin. Invest. 110, 1375-1381 (2002).
3. R. Vassar, B. D. Bennett, S. Babu-Khan, S. Kahn, E. A. Mendiaz, P. Denis, D. B. Teplow, S. Ross, P. Amarante, R. Loeloff, Y. Luo, S. Fisher, J. Fuller, S. Edenson, J. Lile, M. A. Jarosinski, A. L. Biere, E. Curran, T. Burgess, J.-C. Louis, F. Collins, J. Treanor, G. Rogers, M. Citron, β-Secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286, 735-741 (1999).
4. W. T. Kimberly, M. J. LaVoie, B. L. Ostaszewski, W. Ye, M. S. Wolfe, D. J. Selkoe, γ-Secretase is a membrane protein complex comprised of presenilin, nicastrin, aph-1, and pen-2. Proc. Natl. Acad. Sci. U. S. A. 100, 6382-6387 (2003).
5. A. Goate, Segregation of a missense mutation in the amyloid β-protein precursor gene with familial Alzheimer's disease. J. Alzheimers Dis. 9, 341-347 (2006).
6. G. Bu, Apolipoprotein E and its receptors in Alzheimer's disease: Pathways, pathogenesis and therapy. Nat. Rev. Neurosci. 10, 333-344 (2009).
7. L. Mucke, D. J. Selkoe, Neurotoxicity of amyloid β-protein: Synaptic and network dysfunction. Cold Spring Harb. Perspect. Med. 2, a006338 (2012).
8. J. R. Cirrito, P. C. May, M. A. O'Dell, J. W. Taylor, M. Parsadanian, J. W. Cramer, J. E. Audia, J. S. Nissen, K. R. Bales, S. M. Paul, R. B. DeMattos, D. M. Holtzman, In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-β metabolism and half-life. J. Neurosci. 23, 8844-8853 (2003).
9. R. J. Bateman, L. Y. Munsell, J. C. Morris, R. Swarm, K. E. Yarasheski, D. M. Holtzman, Human amyloid-β synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat. Med. 12, 856-861 (2006).
10. K. G. Mawuenyega, W. Sigurdson, V. Ovod, L. Munsell, T. Kasten, J. C. Morris, K. E. Yarasheski, R. J. Bateman, Decreased clearance of CNS β-amyloid in Alzheimer's disease. Science 330, 1774 (2010).
11. P. W. Park, O. Reizes, M. Bernfield, Cell surface heparan sulfate proteoglycans: Selective regulators of ligand-receptor encounters. J. Biol. Chem. 275, 29923-29926 (2000).
12. S. Sarrazin, W. C. Lamanna, J. D. Esko, Heparan sulfate proteoglycans. Cold Spring Harb. Perspect. Biol. 3, a004952 (2011).
13. J. R. Bishop, M. Schuksz, J. D. Esko, Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature 446, 1030-1037 (2007).
14. T. Lind, F. Tufaro, C. McCormick, U. Lindahl, K. Lidholt, The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate. J. Biol. Chem. 273, 26265-26268 (1998).
15. X. Lin, G. Wei, Z. Shi, L. Dryer, J. D. Esko, D. E. Wells, M. M. Matzuk, Disruption of gastrulation and heparan sulfate biosynthesis in EXT1-deficient mice. Dev. Biol. 224, 299-311 (2000).
16. S. L. Cotman, W. Halfter, G. J. Cole, Agrin binds to β-amyloid (Aβ), accelerates Aβ fibril formation, and is localized to Aβ deposits in Alzheimer's disease brain. Mol. Cell. Neurosci. 15, 183-198 (2000).
17. J. Van Horssen, I. Otte-Höller, G. David, M. L. Maat-Schieman, L. P. Van Den Heuvel, P. Wesseling, R. M. De Waal, M. M. Verbeek, Heparan sulfate proteoglycan expression in cerebrovascular amyloid β deposits in Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis (Dutch) brains. Acta Neuropathol. 102, 604-614 (2001).
18. D. Van Gool, G. David, M. Lammens, F. Baro, R. Dom, Heparan sulfate expression patterns in the amyloid deposits of patients with Alzheimer's and Lewy body type dementia. Dementia 4, 308-314 (1993).
19. G.-L. Zhang, X. Zhang, X.-M. Wang, J.-P. Li, Towards understanding the roles of heparan sulfate proteoglycans in Alzheimer's disease. Biomed. Res. Int. 2014, 516028 (2014).
20. N. Watanabe, W. Araki, D.-H. Chui, T. Makifuchi, Y. Ihara, T. Tabira, Glypican-1 as an Aβ binding HSPG in the human brain: Its localization in DIG domains and possible roles in the pathogenesis of Alzheimer's disease. FASEB J. 18, 1013-1015 (2004).
21. F. Cheng, K. Ruscher, L.-Å. Fransson, K. Mani, Non-toxic amyloid beta formed in the presence of glypican-1 or its deaminatively generated heparan sulfate degradation products. Glycobiology 23, 1510-1519 (2013).
22. K. R. Brunden, N. J. Richter-Cook, N. Chaturvedi, R. C. A. Frederickson, pH-dependent binding of synthetic β-amyloid peptides to glycosaminoglycans. J. Neurochem. 61, 2147-2154 (1993).
23. E. Sandwall, P. O'Callaghan, X. Zhang, U. Lindahl, L. Lannfelt, J.-P. Li, Heparan sulfate mediates amyloid-beta internalization and cytotoxicity. Glycobiology 20, 533-541 (2010).
24. L. Bergamaschini, C. Donarini, E. Rossi, A. De Luigi, C. Vergani, M. G. De Simoni, Heparin attenuates cytotoxic and inflammatory activity of Alzheimer amyloid-β in vitro. Neurobiol. Aging 23, 531-536 (2002).
25. T. Kanekiyo, J. Zhang, Q. Liu, C.-C. Liu, L. Zhang, G. Bu, Heparan sulphate proteoglycan and the low-density lipoprotein receptor-related protein 1 constitute major pathways for neuronal amyloid-β uptake. J. Neurosci. 31, 1644-1651 (2011).
26. C. B. Jendresen, H. Cui, X. Zhang, I. Vlodavsky, L. N. G. Nilsson, J.-P. Li, Overexpression of heparanase lowers the amyloid burden in amyloid-β precursor protein transgenic mice. J. Biol. Chem. 290, 5053-5064 (2015).
27. M. Inatani, F. Irie, A. S. Plump, M. Tessier-Lavigne, Y. Yamaguchi, Mammalian brain morphogenesis and midline axon guidance require heparan sulfate. Science 302, 1044-1046 (2003).
28. J. Z. Tsien, D. F. Chen, D. Gerber, C. Tom, E. H. Mercer, D. J. Anderson, M. Mayford, E. R. Kandel, S. Tonegawa, Subregion- and cell type-restricted gene knockout in mouse brain. Cell 87, 1317-1326 (1996).
29. J. L. Jankowsky, D. J. Fadale, J. Anderson, G. M. Xu, V. Gonzales, N. A. Jenkins, N. G. Copeland, M. K. Lee, L. H. Younkin, S. L. Wagner, S. G. Younkin, D. R. Borchelt, Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: Evidence for augmentation of a 42-specific γ secretase. Hum. Mol. Genet. 13, 159-170 (2004).
30. F. Irie, H. Badie-Mahdavi, Y. Yamaguchi, Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate. Proc. Natl. Acad. Sci. U. S. A. 109, 5052-5056 (2012).
31. J. Van Horssen, P. Wesseling, L. P. W. J. Van Den Heuvel, R. M. W. De Waal, M. M. Verbeek, Heparan sulphate proteoglycans in Alzheimer's disease and amyloid-related disorders. Lancet Neurol. 2, 482-492 (2003).
32. P. O'Callaghan, E. Sandwall, J.-P. Li, H. Yu, R. Ravid, Z.-Z. Guan, T. H. Van Kuppevelt, L. N. G. Nilsson, M. Ingelsson, B. T. Hyman, H. Kalimo, U. Lindahl, L. Lannfelt, X. Zhang, Heparan sulfate accumulation with Aβ deposits in Alzheimer's disease and Tg2576 mice is contributed by glial cells. Brain Pathol. 18, 548-561 (2008).
33. M. Garcia-Alloza, E. M. Robbins, S. X. Zhang-Nunes, S. M. Purcell, R. A. Betensky, S. Raju, C. Prada, S. M. Greenberg, B. J. Bacskai, M. P. Frosch, Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease. Neurobiol. Dis. 24, 516-524 (2006).
34. K. L. Youmans, L. M. Tai, T. Kanekiyo, W. B. Stine Jr., S.-C. Michon, E. Nwabuisi-Heath, A. M. Manelli, Y. Fu, S. Riordan, W. A. Eimer, L. Binder, G. Bu, C. Yu, D. M. Hartley, M. J. LaDu, Intraneuronal Aβ detection in 5xFAD mice by a new Aβ-specific antibody. Mol. Neurodegener. 7, 8 (2012).
35. N. M. Timmer, M. K. Herbert, J. W. Kleinovink, A. J. Kiliaan, R. M. W. De Waal, M. M. Verbeek, Limited expression of heparan sulphate proteoglycans associated with Aβ deposits in the APPswe/PS1dE9 mouse model for Alzheimer's disease. Neuropathol. Appl. Neurobiol. 36, 478-486 (2010).
36. M. M. Verbeek, I. Otte-Höller, J. Van Den Born, L. P. W. J. Van Den Heuvel, G. David, P. Wesseling, R. M. W. De Waal, Agrin is a major heparan sulfate proteoglycan accumulating in Alzheimer's disease brain. Am. J. Pathol. 155, 2115-2125 (1999).
37. S. M. Rauch, K. Huen, M. C. Miller, H. Chaudry, M. Lau, J. R. Sanes, C. E. Johanson, E. G. Stopa, R. W. Burgess, Changes in brain β-amyloid deposition and aquaporin 4 levels in response to altered Agrin expression in mice. J. Neuropathol. Exp. Neurol. 70, 1124-1137 (2011).
38. K. L. Youmans, S. Leung, J. Zhang, E. Maus, K. Baysac, G. Bu, R. Vassar, C. Yu, M. J. LaDu, Amyloid-β42 alters apolipoprotein E solubility in brains of mice with five familial AD mutations. J. Neurosci. Methods 196, 51-59 (2011).
39. D. J. Selkoe, Soluble oligomers of the amyloid β-protein impair synaptic plasticity and behavior. Behav. Brain Res. 192, 106-113 (2008).
40. W. Xia, T. Yang, G. Shankar, I. M. Smith, Y. Shen, D. M. Walsh, D. J. Selkoe, A specific enzymelinked immunosorbent assay for measuring β-amyloid protein oligomers in human plasma and brain tissue of patients with Alzheimer disease. Arch. Neurol. 66, 190-199 (2009).
41. G. M. Castillo, W. Lukito, T. N. Wight, A. D. Snow, The sulfate moieties of glycosaminoglycans are critical for the enhancement of β-amyloid protein fibril formation. J. Neurochem. 72, 1681-1687 (1999).
42. T. Wyss-Coray, Inflammation in Alzheimer disease: Driving force, bystander or beneficial response? Nat. Med. 12, 1005-1015 (2006).
43. J. M. Rubio-Perez, J. M. Morillas-Ruiz, A review: Inflammatory process in Alzheimer's disease, role of cytokines. ScientificWorldJournal 2012, 756357 (2012).
44. J. R. Cirrito, B. M. Disabato, J. L. Restivo, D. K. Verges, W. D. Goebel, A. Sathyan, D. Hayreh, G. D'Angelo, T. Benzinger, H. Yoon, J. Kim, J. C. Morris, M. A. Mintun, Y. I. Sheline, Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans. Proc. Natl. Acad. Sci. U. S. A. 108, 14968-14973 (2011).
45. A. W. Bero, P. Yan, J. H. Roh, J. R. Cirrito, F. R. Stewart, M. E. Raichle, J.-M. Lee, D. M. Holtzman, Neuronal activity regulates the regional vulnerability to amyloid-β deposition. Nat. Neurosci. 14, 750-756 (2011).
46. R. O. Weller, M. Subash, S. D. Preston, I. Mazanti, R. O. Carare, Perivascular drainage of amyloid-β peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer's disease. Brain Pathol. 18, 253-266 (2008).
47. A. D. Snow, R. T. Sekiguchi, D. Nochlin, R. N. Kalaria, K. Kimata, Heparan sulfate proteoglycan in diffuse plaques of hippocampus but not of cerebellum in Alzheimer's disease brain. Am. J. Pathol. 144, 337-347 (1994).
48. A. D. Snow, H. Mar, D. Nochlin, K. Kimata, M. Kato, S. Suzuki, J. Hassell, T. N. Wight, The presence of heparan sulfate proteoglycans in the neuritic plaques and congophilic angiopathy in Alzheimer's disease. Am. J. Pathol. 133, 456-463 (1988).
49. J. E. Donahue, T. M. Berzin, M. S. Rafii, D. J. Glass, G. D. Yancopoulos, J. R. Fallon, E. G. Stopa, Agrin in Alzheimer's disease: Altered solubility and abnormal distribution within microvasculature and brain parenchyma. Proc. Natl. Acad. Sci. U. S. A. 96, 6468-6472 (1999).
50. Y. Huang, L. Mucke, Alzheimer mechanisms and therapeutic strategies. Cell 148, 1204-1222 (2012).
51. D. M. Holtzman, J. C. Morris, A. M. Goate, Alzheimer's disease: The challenge of the second century. Sci. Transl. Med. 3, 77sr71 (2011).
52. M. Citron, T. Oltersdorf, C. Haass, L. McConlogue, A. Y. Hung, P. Seubert, C. Vigo-Pelfrey, I. Lieberburg, D. J. Selkoe, Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production. Nature 360, 672-674 (1992).
53. D. Campion, C. Dumanchin, D. Hannequin, B. Dubois, S. Belliard, M. Puel, C. Thomas-Anterion, A. Michon, C. Martin, F. Charbonnier, G. Raux, A. Camuzat, C. Penet, V. Mesnage, M. Martinez, F. Clerget-Darpoux, A. Brice, T. Frebourg, Early-onset autosomal dominant Alzheimer disease: Prevalence, genetic heterogeneity, and mutation spectrum. Am. J. Hum. Genet. 65, 664-670 (1999).
54. R. V. Iozzo, Heparan sulfate proteoglycans: Intricate molecules with intriguing functions. J. Clin. Invest. 108, 165-167 (2001).
55. J. Turnbull, A. Powell, S. Guimond, Heparan sulfate: Decoding a dynamic multifunctional cell regulator. Trends Cell Biol. 11, 75-82 (2001).
56. B. B. Holmes, S. L. DeVos, N. Kfoury, M. Li, R. Jacks, K. Yanamandra, M. O. Ouidja, F. M. Brodsky, J. Marasa, D. P. Bagchi, P. T. Kotzbauer, T. M. Miller, D. Papy-Garcia, M. I. Diamond, Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds. Proc. Natl. Acad. Sci. U. S. A. 110, E3138-E3147 (2013).
57. K. J. Bame, J. Danda, A. Hassall, S. Tumova, Aβ (1-40) prevents heparanase-catalyzed degradation of heparan sulfate glycosaminoglycans and proteoglycans in vitro. A role for heparan sulfate proteoglycan turnover in Alzheimers disease. J. Biol. Chem. 272, 17005-17011 (1997).
58. J. R. Cirrito, R. Deane, A. M. Fagan, M. L. Spinner, M. Parsadanian, M. B. Finn, H. Jiang, J. L. Prior, A. Sagare, K. R. Bales, S. M. Paul, B. V. Zlokovic, D. Piwnica-Worms, D. M. Holtzman, P-glycoprotein deficiency at the blood-brain barrier increases amyloid-β deposition in an Alzheimer disease mouse model. J. Clin. Invest. 115, 3285-3290 (2005).
59. W. Farris, S. G. Schütz, J. R. Cirrito, G. M. Shankar, X. Sun, A. George, M. A. Leissring, D. M. Walsh, W. Q. Qiu, D. M. Holtzman, D. J. Selkoe, Loss of neprilysin function promotes amyloid plaque formation and causes cerebral amyloid angiopathy. Am. J. Pathol. 171, 241-251 (2007).
60. J. S. Miners, S. Baig, J. Palmer, L. E. Palmer, P. G. Kehoe, S. Love, Aβ-degrading enzymes in Alzheimer's disease. Brain Pathol. 18, 240-252 (2008).
61. T. Saido, M. A. Leissring, Proteolytic degradation of amyloid β-protein. Cold Spring Harb. Perspect. Med. 2, a006379 (2012).
62. R. Gupta-Bansal, R. C. A. Frederickson, K. R. Brunden, Proteoglycan-mediated inhibition of Aβ proteolysis. A potential cause of senile plaque accumulation. J. Biol. Chem. 270, 18666-18671 (1995).
63. A. P. Sagare, R. D. Bell, B. V. Zlokovic, Neurovascular dysfunction and faulty amyloid β-peptide clearance in Alzheimer disease. Cold Spring Harb. Perspect. Med. 2, a011452 (2012).
64. T. Kanekiyo, H. Xu, G. Bu, ApoE and Aβ in Alzheimer's disease: Accidental encounters or partners? Neuron 81, 740-754 (2014).
65. L. Bergamaschini, E. Rossi, C. Storini, S. Pizzimenti, M. Distaso, C. Perego, A. De Luigi, C. Vergani, M. G. De Simoni, Peripheral treatment with enoxaparin, a low molecular weight heparin, reduces plaques and β-amyloid accumulation in a mouse model of Alzheimer's disease. J. Neurosci. 24, 4181-4186 (2004).
66. T. Kanekiyo, J. R. Cirrito, C.-C. Liu, M. Shinohara, J. Li, D. R. Schuler, D. M. Holtzman, G. Bu, Neuronal clearance of amyloid-β by endocytic receptor LRP1. J. Neurosci. 33, 19276-19283 (2013).
67. X. Hu, S. L. Crick, G. Bu, C. Frieden, R. V. Pappu, J. M. Lee, Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide. Proc. Natl. Acad. Sci. U. S. A. 106, 20324-20329 (2009).
68. J. Li, T. Kanekiyo, M. Shinohara, Y. Zhang, M. J. LaDu, H. Xu, G. Bu, Differential regulation of amyloid-β endocytic trafficking and lysosomal degradation by apolipoprotein E isoforms. J. Biol. Chem. 287, 44593-44601 (2012).
69. J. C. Watts, C. Condello, J. Stöhr, A. Oehler, J. Lee, S. J. DeArmond, L. Lannfelt, M. Ingelsson, K. Giles, S. B. Prusiner, Serial propagation of distinct strains of Aβ prions from Alzheimer's disease patients. Proc. Natl. Acad. Sci. U. S. A. 111, 10323-10328 (2014).
70. M. Meyer-Luehmann, J. Coomaraswamy, T. Bolmont, S. Kaeser, C. Schaefer, E. Kilger, A. Neuenschwander, D. Abramowski, P. Frey, A. L. Jaton, J.-M. Vigouret, P. Paganetti, D. M. Walsh, P. M. Mathews, J. Ghiso, M. Staufenbiel, L. C. Walker, M. Jucker, Exogenous induction of cerebral β-amyloidogenesis is governed by agent and host. Science 313, 1781-1784 (2006).
71. H.-L. Song, S. Shim, D.-H. Kim, S.-H. Won, S. Joo, S. Kim, N. L. Jeon, S.-Y. Yoon, β-Amyloid is transmitted via neuronal connections along axonal membranes. Ann. Neurol. 75, 88-97 (2014).
72. J. L. Guo, D. J. Covell, J. P. Daniels, M. Iba, A. Stieber, B. Zhang, D. M. Riddle, L. K. Kwong, Y. Xu, J. Q. Trojanowski, V. M. Y. Lee, Distinct α-synuclein strains differentially promote tau inclusions in neurons. Cell 154, 103-117 (2013).
73. M. Futamura, P. Dhanasekaran, T. Handa, M. C. Phillips, S. Lund-Katz, H. Saito, Two-step mechanism of binding of apolipoprotein E to heparin: Implications for the kinetics of apolipoprotein E-heparan sulfate proteoglycan complex formation on cell surfaces. J. Biol. Chem. 280, 5414-5422 (2005).
74. C.-C. Liu, T. Kanekiyo, H. Xu, G. Bu, Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy. Nat. Rev. Neurol. 9, 106-118 (2013).
75. C.-C. Liu, C.-W. Tsai, F. Deak, J. Rogers, M. Penuliar, Y. M. Sung, J. N. Maher, Y. Fu, X. Li, H. Xu, S. Estus, H.-S. Hoe, J. D. Fryer, T. Kanekiyo, G. Bu, Deficiency in LRP6-mediated Wnt signaling contributes to synaptic abnormalities and amyloid pathology in Alzheimer's disease. Neuron 84, 63-77 (2014).
76. K. E. Grear, I.-F. Ling, J. F. Simpson, J. L. Furman, C. R. Simmons, S. L. Peterson, F. A. Schmitt, W. R. Markesbery, Q. Liu, J. E. Crook, S. G. Younkin, G. Bu, S. Estus, Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain. Mol. Neurodegener. 4, 46 (2009).
77. P. Das, C. Verbeeck, L. Minter, P. Chakrabarty, K. Felsenstein, T. Kukar, G. Maharvi, A. Fauq, B. A. Osborne, T. E. Golde, Transient pharmacologic lowering of Aβ production prior to deposition results in sustained reduction of amyloid plaque pathology. Mol. Neurodegener. 7, 39 (2012).
78. W. M. Tay, J. G. Bryant, P. K. Martin, A. J. Nix, B. M. Cusack, T. L. Rosenberry, A mass spectrometric approach for characterization of amyloid-β aggregates and identification of their post-translational modifications. Biochemistry 51, 3759-3766 (2012).
79. V. Rangachari, B. D. Moore, D. K. Reed, L. K. Sonoda, A. W. Bridges, E. Conboy, D. Hartigan, T. L. Rosenberry, Amyloid-β (1-42) rapidly forms protofibrils and oligomers by distinct pathways in low concentrations of sodium dodecylsulfate. Biochemistry 46, 12451-12462 (2007).
80. P. Chakrabarty, C. Ceballos-Diaz, A. Beccard, C. Janus, D. Dickson, T. E. Golde, P. Das, IFN-γ promotes complement expression and attenuates amyloid plaque deposition in amyloid β precursor protein transgenic mice. J. Immunol. 184, 5333-5343 (2010).