Novel Aβ isoforms in alzheimer's disease - their role in diagnosis and treatment

Current Pharmaceutical Design

Volumn 17, Issue 25, 2011, Pages 2594-2602

  Portelius, Erik ^a   Mattsson, Niklas ^a   Andreasson, Ulf ^a   Blennow, Kaj ^a   Zetterberg, Henrik ^a  

^a SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

Alzheimer's disease; Amyloid; App; Biomarker; Theragnostic marker

Indexed keywords

ALPHA SECRETASE; AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-14]; AMYLOID BETA PROTEIN[1-15]; AMYLOID BETA PROTEIN[1-16]; AMYLOID BETA PROTEIN[1-42]; BETA SECRETASE; GAMMA SECRETASE; GAMMA SECRETASE INHIBITOR; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; CEREBROSPINAL FLUID; DIAGNOSTIC VALUE; DRUG TARGETING; HUMAN; NEUROPATHOLOGY; NEUROTOXICITY; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN AGGREGATION; REVIEW;

EID: 80053309666     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161211797416039     Document Type: Review

References (140)

1. Alzheimer A, Stelzmann RA, Schnitzlein HN, Murtagh FR. An English translation of Alzheimer's 1907 paper, Uber eine eigenartige Erkankung der Hirnrinde. Clin Anat 1995; 8(6): 429-31.
2. Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med 2010; 362(4): 329-44.
3. Caselli RJ, Beach TG, Yaari R, Reiman EM. Alzheimer's disease a century later. J Clin Psychiatry 2006; 67(11): 1784-800.
4. Harvey RJ, Skelton-Robinson M, Rossor MN. The prevalence and causes of dementia in people under the age of 65 years. J Neurol Neurosurg Psychiatry 2003; 74(9): 1206-9.
5. Glenner GG, Wong CW. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984; 120(3): 885-90.
6. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 1985; 82(12): 4245-9.
7. Wong CW, Quaranta V, Glenner GG. Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are antigenically related. Proc Natl Acad Sci USA 1985; 82(24): 8729-32.
8. Goldgaber D, Lerman MI, McBride OW, Saffiotti U, Gajdusek DC. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science 1987; 235(4791): 877-80.
9. Kang J, Lemaire HG, Unterbeck A, et al. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 1987; 325(6106): 733-6.
10. Miller DL, Papayannopoulos IA, Styles J, et al. Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer's disease. Arch Biochem Biophys 1993; 301(1): 41-52.
11. Naslund J, Schierhorn A, Hellman U, et al. Relative abundance of Alzheimer A beta amyloid peptide variants in Alzheimer disease and normal aging. Proc Natl Acad Sci USA 1994; 91(18): 8378-82.
12. Portelius E, Bogdanovic N, Gustavsson MK, et al. Mass spectrometric characterization of brain amyloid beta isoform signatures in familial and sporadic Alzheimer's disease. Acta Neuropathol 2010; 120(2): 185-93.
13. Burdick D, Soreghan B, Kwon M, et al. Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs. J Biol Chem 1992; 267(1): 546-54.
14. Jarrett JT, Berger EP, Lansbury PT, Jr. The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease. Biochemistry 1993; 32(18): 4693-7.
15. Seubert P, Vigo-Pelfrey C, Esch F, et al. Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. Nature 1992; 359(6393): 325-7.
16. Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson- Wood K, Galasko D, et al. Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease. Ann Neurol 1995; 38(4): 643-8.
17. Tabaton M, Nunzi MG, Xue R, Usiak M, Autilio-Gambetti L, Gambetti P. Soluble amyloid beta-protein is a marker of Alzheimer amyloid in brain but not in cerebrospinal fluid. Biochem Biophys Res Commun 1994; 200(3): 1598-603.
18. Van Nostrand WE, Wagner SL, Shankle WR, et al. Decreased levels of soluble amyloid beta-protein precursor in cerebrospinal fluid of live Alzheimer disease patients. Proc Natl Acad Sci USA1992; 89(7): 2551-5.
19. Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 2010; 6(3): 131-44.
20. Strozyk D, Blennow K, White LR, Launer LJ. CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology 2003; 60(4): 652-6.
21. Fagan AM, Mintun MA, Mach RH, et al. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol 2006; 59(3): 512-9.
22. Degerman Gunnarsson M, Lindau M, Wall A, et al. Pittsburgh compound-B and Alzheimer's disease biomarkers in CSF, plasma and urine: An exploratory study. Dement Geriatr Cogn Disord 2010; 29(3): 204-12.
23. Portelius E, Zetterberg H, Gobom J, Andreasson U, Blennow K. Targeted proteomics in Alzheimer's disease: focus on amyloid-beta. Expert Rev Proteomics 2008; 5(2): 225-37.
24. Wang R, Sweeney D, Gandy SE, Sisodia SS. The profile of soluble amyloid beta protein in cultured cell media. Detection and quantification of amyloid beta protein and variants by immunoprecipitation-mass spectrometry. J Biol Chem 1996; 271(50): 31894-902.
25. Wasling P, Daborg J, Riebe I, et al. Synaptic retrogenesis and amyloid-beta in Alzheimer's disease. J Alzheimers Dis 2009; 16(1): 1-14.
26. Giliberto L, d'Abramo C, Acker CM, Davies P, D'Adamio L. Transgenic expression of the amyloid-beta precursor proteinintracellular domain does not induce Alzheimer's Disease-like traits in vivo. PLoS One 2010; 5(7): e11609.
27. Li H, Wang B, Wang Z, Guo Q, Tabuchi K, Hammer RE, et al. Soluble amyloid precursor protein (APP) regulates transthyretin and Klotho gene expression without rescuing the essential function of APP. Proc Natl Acad Sci USA 2010; 107(40): 17362-7.
28. Soscia SJ, Kirby JE, Washicosky KJ, et al. The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One 2010; 5(3): e9505.
29. Vassar R, Bennett BD, Babu-Khan S, et al. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 1999; 286(5440): 735-41.
30. Hook V, Toneff T, Bogyo M, et al. Inhibition of cathepsin B reduces beta-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate beta-secretase of Alzheimer's disease. Biol Chem 2005; 386(9): 931-40.
31. Beher D, Wrigley JD, Owens AP, Shearman MS. Generation of Cterminally truncated amyloid-beta peptides is dependent on gamma-secretase activity. J Neurochem 2002; 82(3): 563-75.
32. Portelius E, Price E, Brinkmalm G, et al. A novel pathway for amyloid precursor protein processing. Neurobiol Aging 2011; 32(6): 1090-8.
33. Selkoe DJ, Wolfe MS. Presenilin: running with scissors in the membrane. Cell 2007; 131(2): 215-21.
34. Zhao G, Liu Z, Ilagan MX, Kopan R. Gamma-secretase composed of PS1/Pen2/Aph1a can cleave notch and amyloid precursor protein in the absence of nicastrin. J Neurosci 2010; 30(5): 1648-56.
35. Kopan R, Ilagan MX. Gamma-secretase: proteasome of the membrane? Nat Rev Mol Cell Biol 2004; 5(6): 499-504.
36. Esch FS, Keim PS, Beattie EC, et al. Cleavage of amyloid beta peptide during constitutive processing of its precursor. Science 1990; 248(4959): 1122-4.
37. Lammich S, Kojro E, Postina R, et al. Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease. Proc Natl Acad Sci USA 1999; 96(7): 3922-7.
38. Haass C, Schlossmacher MG, Hung AY, et al. Amyloid betapeptide is produced by cultured cells during normal metabolism. Nature 1992; 359(6393): 322-5.
39. Gowing E, Roher AE, Woods AS, et al. Chemical characterization of A beta 17-42 peptide, a component of diffuse amyloid deposits of Alzheimer disease. J Biol Chem 1994; 269(15): 10987-90.
40. Lalowski M, Golabek A, Lemere CA, et al. Thenonamyloidogenic p3 fragment (amyloid beta17-42) is a major constituent of Down's syndrome cerebellar preamyloid. J Biol Chem 1996; 271(52): 33623-31.
41. Haass C, Hung AY, Schlossmacher MG, Teplow DB, Selkoe DJ. beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms. J Biol Chem 1993; 268(5): 3021-4.
42. Gouras GK, Xu H, Jovanovic JN, et al. Generation and regulation of beta-amyloid peptide variants by neurons. J Neurochem 1998; 71(5): 1920-5.
43. Sharples RA, Vella LJ, Nisbet RM, et al. Inhibition of gammasecretase causes increased secretion of amyloid precursor protein C-terminal fragments in association with exosomes. FASEB J 2008; 22(5): 1469-78.
44. Kuhn PH, Wang H, Dislich B, et al. ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons. EMBO J 2010; 29(17): 3020-32.
45. Portelius E, Zhang B, Gustavsson MK, et al. Effects of gammasecretase inhibition on the amyloid beta isoform pattern in a mouse model of Alzheimer's disease. Neurodegener Dis 2009; 6(5-6): 258-62.
46. Portelius E, Van Broeck B, Andreasson U, et al. Acute effect on the Abeta isoform pattern in CSF in response to gamma-secretase modulator and inhibitor treatment in dogs. J Alzheimers Dis 2010; 21(3): 1005-12.
47. Cook JJ, Wildsmith KR, Gilberto DB, et al. Acute gammasecretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-beta production to alternative APP fragments without amyloid-beta rebound. J Neurosci 2010; 30(19): 6743-50.
48. Portelius E, Dean RA, Gustavsson MK, et al. A novel Abeta isoform pattern in CSF reflects gamma-secretase inhibition in Alzheimer disease. Alzheimers Res Ther 2010; 2(2): 7.
49. De Strooper B. Proteases and proteolysis in Alzheimer disease: a multifactorial view on the disease process. Physiol Rev 2010; 90(2): 465-94.
50. Howell S, Nalbantoglu J, Crine P. Neutral endopeptidase can hydrolyze beta-amyloid(1-40) but shows no effect on beta-amyloid precursor protein metabolism. Peptides 1995; 16(4): 647-52.
51. Iwata N, Tsubuki S, Takaki Y, et al. Metabolic regulation of brain Abeta by neprilysin. Science 2001; 292(5521): 1550-2.
52. Miners JS, Baig S, Tayler H, Kehoe PG, Love S. Neprilysin and insulin-degrading enzyme levels are increased in Alzheimer disease in relation to disease severity. J Neuropathol Exp Neurol 2009; 68(8): 902-14.
53. Palmer JC, Baig S, Kehoe PG, Love S. Endothelin-converting enzyme-2 is increased in Alzheimer's disease and up-regulated by Abeta. Am J Pathol 2009; 175(1): 262-70.
54. Tucker HM, Kihiko-Ehmann M, Wright S, Rydel RE, Estus S. Tissue plasminogen activator requires plasminogen to modulate amyloid-beta neurotoxicity and deposition. J Neurochem 2000; 75(5): 2172-7.
55. Van Nostrand WE, Porter M. Plasmin cleavage of the amyloid beta-protein: alteration of secondary structure and stimulation of tissue plasminogen activator activity. Biochemistry 1999; 38(35): 11570-6.
56. Ledesma MD, Da Silva JS, Crassaerts K, Delacourte A, De Strooper B, Dotti CG. Brain plasmin enhances APP alpha-cleavage and Abeta degradation and is reduced in Alzheimer's disease brains. EMBO Rep 2000; 1(6): 530-5.
57. Andreasson U, Portelius E, Andersson ME, Blennow K, Zetterberg H. Aspects of beta-amyloid as a biomarker for Alzheimer's disease. Biomarkers in Medicine 2007; 1(1): 59-78.
58. Shibata M, Yamada S, Kumar SR, et al. Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest 2000; 106(12): 1489-99.
59. Moir RD, Tanzi RE. LRP-mediated clearance of Abeta is inhibited by KPI-containing isoforms of APP. Curr Alzheimer Res 2005; 2(2): 269-73.
60. DeMattos RB, Bales KR, Cummins DJ, Paul SM, Holtzman DM. Brain to plasma amyloid-beta efflux: a measure of brain amyloid burden in a mouse model of Alzheimer's disease. Science 2002; 295(5563): 2264-7.
61. DeMattos RB, Bales KR, Parsadanian M, et al. Plaque-associated disruption of CSF and plasma amyloid-beta (Abeta) equilibrium in a mouse model of Alzheimer's disease. J Neurochem 2002; 81(2): 229-36.
62. Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993; 261(5123): 921-3.
63. Poirier J, Davignon J, Bouthillier D, Kogan S, Bertrand P, Gauthier S. Apolipoprotein E polymorphism and Alzheimer's disease. Lancet 1993; 342(8873): 697-9.
64. Raber J, Huang Y, Ashford JW. ApoE genotype accounts for the vast majority of AD risk and AD pathology. Neurobiol Aging 2004; 25(5): 641-50.
65. Morris JC, Roe CM, Xiong C, et al. APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol 2010; 67(1): 122-31.
66. Stern Y. Cognitive reserve and Alzheimer disease. Alzheimer Dis Assoc Disord 2006; 20(2): 112-7.
67. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984; 34(7): 939-44.
68. Jellinger KA. Alzheimer 100--highlights in the history of Alzheimer research. J Neural Transm 2006; 113(11): 1603-23.
69. Blennow K, Zetterberg H. Is it time for biomarker-based diagnostic criteria for prodromal Alzheimer's disease? Alzheimers Res Ther 2010; 2(2): 8.
70. Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science 1992; 256(5054): 184-5.
71. Lemere CA, Blusztajn JK, Yamaguchi H, Wisniewski T, Saido TC, Selkoe DJ. Sequence of deposition of heterogeneous amyloid betapeptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation. Neurobiol Dis 1996; 3(1): 16-32.
72. Rovelet-Lecrux A, Hannequin D, Raux G, et al. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet 2006; 38(1): 24-6.
73. Theuns J, Brouwers N, Engelborghs S, et al. Promoter mutations that increase amyloid precursor-protein expression are associated with Alzheimer disease. Am J Hum Genet 2006; 78(6): 936-46.
74. Lesne S, Koh MT, Kotilinek L, et al. A specific amyloid-beta protein assembly in the brain impairs memory. Nature 2006; 440(7082): 352-7.
75. Klyubin I, Walsh DM, Lemere CA, et al. Amyloid beta protein immunotherapy neutralizes Abeta oligomers that disrupt synaptic plasticity in vivo. Nat Med 2005; 11(5): 556-61.
76. Giannakopoulos P, Herrmann FR, Bussiere T, et al. Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 2003; 60(9): 1495-500.
77. Mackenzie IR, McLachlan RS, Kubu CS, Miller LA. Prospective neuropsychological assessment of nondemented patients with biopsy proven senile plaques. Neurology 1996; 46(2): 425-9.
78. Jellinger KA. Traumatic brain injury as a risk factor for Alzheimer's disease. J Neurol Neurosurg Psychiatry 2004; 75(3): 511-2.
79. Goate A, Chartier-Harlin MC, Mullan M, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 1991; 349(6311): 704-6.
80. Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 2001; 81(2): 741-66.
81. Brouwers N, Sleegers K, Van Broeckhoven C. Molecular genetics of Alzheimer's disease: an update. Ann Med 2008; 40(8): 562-83.
82. Levy-Lahad E, Wasco W, Poorkaj P, et al. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science 1995; 269(5226): 973-7.
83. Sherrington R, Rogaev EI, Liang Y, et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 1995; 375(6534): 754-60.
84. Bentahir M, Nyabi O, Verhamme J, et al. Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms. J Neurochem 2006; 96(3): 732-42.
85. Kumar-Singh S, Theuns J, Van Broeck B, et al. Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40. Hum Mutat 2006; 27(7): 686-95.
86. Citron M, Westaway D, Xia W, et al. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nat Med 1997; 3(1): 67-72.
87. Ringman JM, Younkin SG, Pratico D, et al. Biochemical markers in persons with preclinical familial Alzheimer disease. Neurology 2008; 71(2): 85-92.
88. Leissring MA. Proteolytic degradation of the amyloid beta-protein: the forgotten side of Alzheimer's disease. Curr Alzheimer Res 2006; 3(5): 431-5.
89. Mehta PD, Pirttila T, Mehta SP, Sersen EA, Aisen PS, Wisniewski HM. Plasma and cerebrospinal fluid levels of amyloid beta proteins 1-40 and 1-42 in Alzheimer disease. Arch Neurol 2000; 57(1): 100-5.
90. Hansson O, Zetterberg H, Buchhave P, et al. Prediction of Alzheimer's disease using the CSF Abeta42/Abeta40 ratio in patients with mild cognitive impairment. Dement Geriatr Cogn Disord 2007; 23(5): 316-20.
91. Lewczuk P, Esselmann H, Meyer M, et al. The amyloid-beta (Abeta) peptide pattern in cerebrospinal fluid in Alzheimer's disease: evidence of a novel carboxyterminally elongated Abeta peptide. Rapid Commun Mass Spectrom 2003; 17(12): 1291-6.
92. Schoonenboom NS, Mulder C, Van Kamp GJ, et al. Amyloid beta 38, 40, and 42 species in cerebrospinal fluid: more of the same? Ann Neurol 2005; 58(1): 139-42.
93. Zellner M, Veitinger M, Umlauf E. The role of proteomics in dementia and Alzheimer's disease. Acta Neuropathol 2009; 118(1): 181-95.
94. Portelius E, Westman-Brinkmalm A, Zetterberg H, Blennow K. Determination of beta-amyloid peptide signatures in cerebrospinal fluid using immunoprecipitation-mass spectrometry. J Proteome Res 2006; 5(4): 1010-6.
95. Portelius E, Brinkmalm G, Tran AJ, Zetterberg H, Westman- Brinkmalm A, Blennow K. Identification of novel APP/Abeta isoforms in human cerebrospinal fluid. Neurodegener Dis 2009; 6(3): 87-94.
96. Simons M, de Strooper B, Multhaup G, Tienari PJ, Dotti CG, Beyreuther K. Amyloidogenic processing of the human amyloid precursor protein in primary cultures of rat hippocampal neurons. J Neurosci 1996; 16(3): 899-908.
97. Weidemann A, Eggert S, Reinhard FB, et al. A novel epsiloncleavage within the transmembrane domain of the Alzheimer amyloid precursor protein demonstrates homology with Notch processing. Biochemistry 2002; 41(8): 2825-35.
98. Portelius E, Brinkmalm G, Tran A, et al. Identification of novel Nterminal fragments of amyloid precursor protein in cerebrospinal fluid. Exp Neurol 2010; 223(2): 351-8.
99. Klyubin I, Betts V, Welzel AT, et al. Amyloid beta protein dimercontaining human CSF disrupts synaptic plasticity: prevention by systemic passive immunization. J Neurosci 2008; 28(16): 4231-7.
100. Fukumoto H, Tokuda T, Kasai T, et al. High-molecular-weight{beta}-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients. FASEB J. 2010: fj.09-150359.
101. Blennow K, Hampel H. CSF markers for incipient Alzheimer's disease. Lancet Neurol 2003; 2(10): 605-13.
102. Blennow K. Cerebrospinal fluid protein biomarkers for Alzheimer's disease. NeuroRx 2004; 1(2): 213-25.
103. Vanderstichele H, De Meyer G, Andreasen N, et al. Aminotruncated beta-amyloid42 peptides in cerebrospinal fluid and prediction of progression of mild cognitive impairment. Clin Chem 2005; 51(9): 1650-60.
104. Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 2006; 5(3): 228-34.
105. Mattsson N, Zetterberg H, Hansson O, et al. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 2009; 302(4): 385-93.
106. Wiltfang J, Esselmann H, Bibl M, et al. Highly conserved and disease-specific patterns of carboxyterminally truncated Abeta peptides 1-37/38/39 in addition to 1-40/42 in Alzheimer's disease and in patients with chronic neuroinflammation. J Neurochem 2002; 81(3): 481-96.
107. Brys M, Pirraglia E, Rich K, et al. Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment. Neurobiol Aging 2009; 30(5): 682-90.
108. Bibl M, Mollenhauer B, Esselmann H, et al. CSF amyloid-betapeptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia. Brain 2006; 129(Pt 5): 1177-87.
109. Cohen SL. Ozone in ambient air as a source of adventitious oxidation. A mass spectrometric study. Anal Chem 2006; 78(13): 4352-62.
110. Portelius E, Zetterberg H, Andreasson U, Brinkmalm G, Andreasen N, Wallin A, et al. An Alzheimer's disease-specific beta-amyloid fragment signature in cerebrospinal fluid. Neurosci Lett 2006; 409(3): 215-9.
111. Portelius E, Andreasson U, Ringman JM, et al. Distinct cerebrospinal fluid amyloid beta peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease. Mol Neurodegener 2010; 5: 2.
112. Lewczuk P, Kamrowski-Kruck H, Peters O, et al. Soluble amyloid precursor proteins in the cerebrospinal fluid as novel potential biomarkers of Alzheimer's disease: a multicenter study. Mol Psychiatry 2010; 15(2): 138-45.
113. Olsson A, Hoglund K, Sjogren M, et al. Measurement of alphaand beta-secretase cleaved amyloid precursor protein in cerebrospinal fluid from Alzheimer patients. Exp Neurol 2003; 183(1): 74-80.
114. Zetterberg H, Andreasson U, Hansson O, et al. Elevated cerebrospinal fluid BACE1 activity in incipient Alzheimer disease. Arch Neurol 2008; 65(8): 1102-7.
115. Nikolaev A, McLaughlin T, O'Leary DD, Tessier-Lavigne M. APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 2009; 457(7232): 981-9.
116. Zetterberg H. Is plasma amyloid-beta a reliable biomarker for Alzheimer's disease? Recent Pat CNS Drug Discov 2008; 3(2): 109-11.
117. Sagare A, Deane R, Bell RD, et al. Clearance of amyloid-beta by circulating lipoprotein receptors. Nat Med 2007; 13(9): 1029-31.
118. Biere AL, Ostaszewski B, Stimson ER, Hyman BT, Maggio JE, Selkoe DJ. Amyloid beta-peptide is transported on lipoproteins and albumin in human plasma. J Biol Chem 1996; 271(51): 32916-22.
119. Vanderstichele H, Van Kerschaver E, Hesse C, et al. Standardization of measurement of beta-amyloid(1-42) in cerebrospinal fluid and plasma. Amyloid 2000; 7(4): 245-58.
120. Scheuner D, Eckman C, Jensen M, et al. Secreted amyloid betaprotein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nat Med 1996; 2(8): 864-70.
121. Vellas B. Use of biomarkers in Alzheimer's trials. J Nutr Health Aging 2009; 13(4): 331.
122. Best JD, Smith DW, Reilly MA, et al. The novel gamma secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl) cyclohexyl]-1,1, 1-trifluoromethanesulfonamide (MRK-560) reduces amyloid plaque deposition without evidence of notchrelated pathology in the Tg2576 mouse. J Pharmacol Exp Ther 2007; 320(2): 552-8.
123. Cirrito JR, May PC, O'Dell MA, et al. In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life. J Neurosci 2003; 23(26): 8844-53.
124. Dovey HF, John V, Anderson JP, et al. Functional gammasecretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem 2001; 76(1): 173-81.
125. Blennow K, de Leon MJ, Zetterberg H. Alzheimer's disease. Lancet 2006; 368(9533): 387-403.
126. Fleisher AS, Raman R, Siemers ER, et al. Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease. Arch Neurol 2008; 65(8): 1031-8.
127. Bateman RJ, Munsell LY, Morris JC, Swarm R, Yarasheski KE, Holtzman DM. Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat Med 2006; 12(7): 856-61.
128. Lannfelt L, Blennow K, Zetterberg H, et al. Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol 2008; 7(9): 779-86.
129. Kadir A, Andreasen N, Almkvist O, et al. Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease. Ann Neurol 2008; 63(5): 621-31.
130. Wyss-Coray T. Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med 2006; 12(9): 1005-15.
131. McGeer PL, McGeer EG. Inflammation, autotoxicity and Alzheimer disease. Neurobiol Aging 2001; 22(6): 799-809.
132. Mattsson N, Axelsson M, Haghighi S, et al. Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis. Mult Scler 2009.
133. Gisslen M, Krut J, Andreasson U, et al. Amyloid and tau cerebrospinal fluid biomarkers in HIV infection. BMC Neurol 2009; 9: 63.
134. Mattsson N, Bremell D, Anckarsater R, Blennow K, Anckarsater H, Zetterberg H, et al. Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism. BMC Neurol 2010; 10: 51.
135. Brew BJ, Pemberton L, Blennow K, Wallin A, Hagberg L. CSF amyloid beta42 and tau levels correlate with AIDS dementia complex. Neurology 2005; 65(9): 1490-2.
136. Sjogren M, Gisslen M, Vanmechelen E, Blennow K. Low cerebrospinal fluid beta-amyloid 42 in patients with acute bacterial meningitis and normalization after treatment. Neurosci Lett 2001; 314(1-2): 33-6.
137. de Leon MJ, Mosconi L, Blennow K, et al. Imaging and CSF studies in the preclinical diagnosis of Alzheimer's disease. Ann N Y Acad Sci 2007; 1097: 114-45.
138. Mathis CA, Bacskai BJ, Kajdasz ST, et al. A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain. Bioorg Med Chem Lett 2002; 12(3): 295-8.
139. Klunk WE, Wang Y, Huang GF, Debnath ML, Holt DP, Mathis CA. Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain. Life Sci 2001; 69(13): 1471-84.
140. Anderson JJ, Holtz G, Baskin PP, et al. Reductions in beta-amyloid concentrations in vivo by the gamma-secretase inhibitors BMS-289948 and BMS-299897. Biochem Pharmacol 2005; 69(4): 689-98.