Developing predictive CSF biomarkers - A challenge critical to success in Alzheimer's disease and neuropsychiatric translational medicine

Biochemical Pharmacology

Volumn 81, Issue 12, 2011, Pages 1422-1434

  Flood, Dorothy G ^a,d   Marek, Gerard J ^b   Williams, Michael ^c  

^a CEPHALON INC   (United States)

^b ABBOTT LABORATORIES   (United States)

^c NORTHWESTERN UNIVERSITY   (United States)

^d EnVivo Pharmaceuticals Inc   (United States)

Author keywords

Alzheimer's disease; CSF biomarkers; Depression; Drug discovery; Parkinson's disease; Schizophrenia

Indexed keywords

ALPHA 1 ANTICHYMOTRYPSIN; ALPHA 1 ANTITRYPSIN; ALPHA 2 MACROGLOBULIN; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; ANTIBIOTIC AGENT; ANTIINFECTIVE AGENT; BIOLOGICAL MARKER; CATHEPSIN B; COMPLEMENT; CREATININE; DIMEBON; DONEPEZIL; ENOLASE; GALANTAMINE; HEAT SHOCK PROTEIN; MEMANTINE; RIVASTIGMINE; SEMAGACESTAT; TARENFLURBIL; TAU PROTEIN;

ALZHEIMER DISEASE; CEREBROSPINAL FLUID; CLINICAL TRIAL (TOPIC); DEPRESSION; DISEASE COURSE; HUMAN; MULTIPLE SCLEROSIS; NEUROPSYCHIATRY; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; SCHIZOPHRENIA; TRANSGENICS; VALIDATION PROCESS; WILD TYPE;

ALZHEIMER DISEASE; ANIMALS; BIOLOGICAL MARKERS; CENTRAL NERVOUS SYSTEM AGENTS; DISEASE MODELS, ANIMAL; HUMANS; NEUROPSYCHIATRY; TRANSLATIONAL RESEARCH;

EID: 79955438992     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2011.01.021     Document Type: Review

References (202)

1. M. Ni The yellow emperor's classic of medicine: a new translation of the Neijing Suwen with commentary 1995 Shambhala Boston, MA
2. P.U. Unschuld, Huang Di, Nei Jing, and Su Wen Nature, knowledge, imagery in an ancient Chinese medical text 2003 University of California Press Berkeley
3. A. Weil Health and healing: the philosophy of integrative medicine 2004 Mariner Books New York pp. 153
4. I. Wilkinson History of clinical chemistry. Wohler and the birth of clinical chemistry J Int Fed Clin Chem Lab Med 13 4 2010 http://www.ifcc.org/ ejifcc/vol13no4/130304003.htm. [Accessed 12/11/10]
5. A.L. Baert Encyclopedia of diagnostic imaging 2008 Springer-Verlag Berlin
6. Biomarkers Definitions Working Group Biomarkers and surrogate endpoints: preferred definitions and conceptual framework Clin Pharmacol Ther 69 2001 89 95
7. P. Rolan The contribution of clinical pharmacology surrogates and models to drug development - a critical review Br J Clin Pharmacol 44 1997 219 225 (Pubitemid 27376248)
8. J. Gabrielson, and D. Weiner Pharmacokinetic and pharmacodynamic data analysis: concepts and applications 4th ed. 2007 Swedish Pharmaceutical Press Stockholm
9. E.I. Ette, and P.J. Williams Pharmacometrics. The science of quantitative pharmacology 2007 Wiley-Interscience Hoboken, NJ
10. T.P. Kenakin A pharmacology primer. Theory, applications, and methods 3rd ed. 2009 Academic Press Burlington, MA
11. R.A. Copeland, Pompliano Dl, and T.D. Meek Drug-target residence time and its implications for lead optimization Nat Rev Drug Discov 5 2006 730 739 (Pubitemid 44323700)
12. A.M. Garber, and W.S. Browner Clinical guideline, part 1: guidelines for using serum cholesterol, high-density lipoprotein cholesterol, and triglyceride levels as screening tests for preventing coronary heart disease in adults Ann Intern Med 124 1996 515 517 (Pubitemid 26070121)
13. S.M. Grundy, J.I. Cleeman, C.N. Merz, H.B. Brewer Jr., L.T. Clark, and D.B. Hunninghake Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines Circulation 110 2004 227 239 (Pubitemid 38924592)
14. Scandinavian Simvastatin Survival Study Group Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) Lancet 344 1994 1383 1389
15. Heart Protection Study Collaborative Group MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial Lancet 360 2002 7 22
16. R. Frank, and R. Hargreaves Clinical biomarkers in drug discovery and development Nat Rev Drug Discov 2 2003 566 580 (Pubitemid 37361748)
17. S.A. Williams, D.E. Slavin, J.A. Wagner, and C.J. Webster A cost-effectiveness approach to the qualification and acceptance of biomarkers Nat Rev Drug Discov 5 2006 897 902 (Pubitemid 44660603)
18. A.S. Ptolemy, and N. Rifai What is a biomarker? Research investments and lack of clinical integration necessitate a review of biomarker terminology and validation schema Scan J Clin Lab Invest 70 Suppl. 242 2010 6 14
19. F.M. Goodsaid, and D.L. Mendrick Translational medicine and the value of biomarker qualification Sci Trans Med 2 47 2010 44
20. D.M. Lloyd-Jones, K. Liu, L. Tian, and P. Greenland Narrative review: assessment of C-reactive protein in risk prediction for cardiovascular disease Ann Intern Med 145 2006 35 42 (Pubitemid 46780605)
21. J. Zacho, A. Tybjaerg-Hansen, J.S. Jensen, P. Grande, H. Sillesen, and B.G. Nordestgaard Genetically elevated C-reactive protein and ischemic vascular disease N Engl J Med 359 2008 1897 1908
22. P.M. Ridker Inflammation high-sensitivity C-reactive protein, and vascular protection Tex Heart Inst J 37 2010 40 41
23. R.G. Katz Biomarkers and surrogate markers: an FDA perspective NeuroRx 1 2004 189 195
24. Eck SL, and Paul SM. Biomarker qualification via Public-Private partnerships Clin Pharmacol Ther 87 2010 21 23
25. J.A. Wagner, M. Prince, E.C. Wright, M.M. Ennis, J. Kochan, and D.J. Nunez The biomarkers consortium: practice and pitfalls of open-source precompetitive collaboration Clin Pharmacol Ther 87 2010 539 542
26. I. Kola, and J. Landis Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3 2004 711 715 (Pubitemid 39173511)
27. B. Munos Lessons from 60 years of pharmaceutical innovation Nat Rev Drug Discov 8 2009 959 968
28. F. Goodsaid, and F. Freuh Biomarker qualification pilot process at the US food and drug administration AAPS J 9 2007 E105 E107
29. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER) Guidance for industry: S7B nonclinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals 2005 http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/ucm074963.pdf
30. R.D. Porsolt, S. Picard, and P. Lacroix International safety pharmacology guidelines (ICH S7A and S7B): where do we go from here? Drug Dev Res 64 2005 83 89 (Pubitemid 40756861)
31. G.A. Gintant, Z. Su, R.L. Martin, and B.F. Cox Utility of hERG assays as surrogate markers of delayed cardiac repolarization and QT safety Toxicol Pathol 34 2006 81 90 (Pubitemid 43323264)
32. J.C. Hancox, M.J. McPate, A. El Harchi, and Y.H. Zhang The hERG potassium channel and hERG screening for drug-induced torsades de pointes Pharmacol Ther 119 2008 118 132
33. Gintant GA An evaluation of hERG current assay performance: translating preclinical safety studies to clinical QT prolongation Pharmacol Ther 129 2011 109 119
34. E.F Schmid, and D.A. Smith Keynote review: is declining innovation in the pharmaceutical industry a myth? Drug Discov Today 10 2005 1031 1039 (Pubitemid 41074141)
35. W.R. Foster, S.U. Ruepp, and B.N. Car Nonclinical toxicogenomics in the pharmaceutical environment Ann Rep Med Chem 44 2008 555 573
36. R.S. Obach, R.L. Walsky, K. Venkatakrishnan, E.A. Gaman, J.B. Houston, and L.M. Tremaine The utility of in vitro cytochrome P450 inhibition data in the prediction of drug-drug interactions J Pharmacol Exp Ther 316 2006 336 348 (Pubitemid 41832613)
37. J.H. Lin CYP induction-mediated drug interactions: in vitro assessment and clinical implications Pharm Res 23 2006 1089 1116 (Pubitemid 43946134)
38. H. Pang, A. Lin, M. Holford, B.E. Enerson, B. Lu, and M.P. Lawton Pathway analysis using random forests classification and regression Bioinformatics 22 2006 2028 2036 (Pubitemid 44283016)
39. D.J. Johann Jr., M.D. McGuigan, A.R. Patel, S. Tomov, S. Ross, and T.P. Conrads Clinical proteomics and biomarker discovery Ann NY Acad Sci 1022 2004 295 305 (Pubitemid 38951617)
40. Y.S. Kim, P. Maruvada, and J.A. Milner Metabolomics in biomarker discovery: future uses for cancer prevention Future Oncol 4 2008 93 102 (Pubitemid 351372610)
41. M. Bogdanov, W.R. Matson, L. Wang, T. Matson, R. Saunders-Pullman, and S.S. Bressman Metabolomic profiling to develop blood biomarkers for Parkinson's disease Brain 131 2008 389 396 (Pubitemid 351197614)
42. B.C. Collins, A. Clarke, N.R. Kitteringham, W.M. Gallagher, and S.R. Pennington Use of proteomics for the discovery of early markers of drug toxicity Exp Opin Drug Metab Toxicol 3 2007 689 704 (Pubitemid 351320637)
43. S. Pettit, S.A. des Etages, L. Mylecraine, R. Snyder, J. Fostel, and R.T. Dunn 2nd Current and future applications of toxicogenomics: results summary of a survey from the HESI genomics state of science subcommittee Environ Health Perspect 118 2010 992 997
44. S.J. Shukla, R. Ruili Huang, C.P. Austin, and M. Xia Foundation review: the future of toxicity testing: a focus on in vitro methods using a quantitative high-throughput screening platform Drug Discov Today 15 2010 997 1007
45. L. Suter, L.E. Babiss, and E.B. Wheeldon Toxicogenomics in predictive toxicology in drug development Chem Biol 11 2004 161 171 (Pubitemid 38300287)
46. J.K. Leighton, P. Brown, A. Ellis, P. Harlow, W. Harrouk, and P.S. Pine Workgroup report: review of genomics data based on experience with mock submissions-view of the CDER Pharmacology Toxicology Nonclinical Pharmacogenomics Subcommittee Environ Health Perspect 114 2006 573 578
47. B. Gomez-Mancilla, E. Marrer, J. Kehren, A. Kinnunen, G. Imbert, and R. Hillebrand Central nervous system drug development: an integrative biomarker approach toward individualized medicine NeuroRx 2 2005 683 695 (Pubitemid 41393275)
48. M.S. Ritsner The handbook of neuropsychiatric biomarkers endophenotypes and genes volume IV: molecular genetic and genomic markers 2009 Springer New York
49. N.J. Romeo, V. Espina, M. Lowenthal, B.H. Espina, E.F. Petricoin III, and L.A. Liotta CSF proteome: a protein repository for potential biomarker identification Exp Rev Proteomics 2 2005 57 70 (Pubitemid 40292580)
50. A.J. Friedhoff, and E.V. Winkle Isolation and characterization of a compound from the urine of schizophrenics Nature 194 1962 897 898
51. A.A. Boulton, and C.A. Felton The "Pink Spot" and Schizophrenia Nature 211 1966 1404 1405
52. M.D. Lindner, D.D. Gordon, J.M. Miller, P.N. Tariot, K.D. McDaniel, and R.W. Hamill Increased levels of truncated nerve growth factor receptor in urine of mildly demented patients with Alzheimer's disease Arch Neurol 50 1993 1054 1060
53. M. Messripour, and A. Mesripour Increased levels of truncated nerve growth factor receptors in congestive heart failure Res J Med Med Sci 4 2009 452 455
54. M.J. During, D.D. Spencer, and Adenosine A potential mediator of seizure arrest and postictal refractoriness Ann Neurol 32 1992 618 624
55. T.S. Maurer, D.B. DeBartolo, D.A. Tess, and D.O. Scott Relationship between exposure and nonspecific binding of thirty-three central nervous system drugs in mice Drug Metab Dispos 33 2005 175 181 (Pubitemid 40023529)
56. H. Tumani, C. Teunissen, S. Sussmuth, M. Otto, A.C. Ludolph, and J. Brettschneider Cerebrospinal fluid biomarkers of neurodegeneration in chronic neurological diseases Exp Rev Mol Diagn 8 2008 479 494 (Pubitemid 351962092)
57. V. Josserand, H. Pélerin, B. de Bruin, B. Jego, B. Kuhnast, and F. Hinnen Evaluation of drug penetration into the brain: a double study by in vivo imaging with positron emission tomography using an in vitro model of the human blood-brain barrier Pharmacol Exp Ther J 316 2006 79 86 (Pubitemid 41832583)
58. D.D. Shen, A.A. Artru, and AdkisonF K.K. Principles and applicability of CSF sampling for the assessment of CNS drug delivery and pharmacodynamics Adv Drug Deliv Rev 56 2004 1825 1857 (Pubitemid 39307054)
59. S.V. Ahmed, C. Jayawarna, and E. Jude Post lumbar puncture headache: diagnosis and management Postgrad Med J 82 2006 713 716
60. K. Arendt, B.M. Demaerschalk, D.M. Wingerchuk, and W. Camann Atraumatic lumbar puncture needles: after all these years, are we still missing the point? Neurologist 15 2009 17 20
61. P. Lewczuk, G. Beck, O. Ganslandt, H. Esselmann, F. Deisenhammer, and A. Regeniter International quality control survey of neurochemical dementia diagnostics Neurosci Lett 409 2006 1 4 (Pubitemid 44740057)
62. Central Nervous System (CNS). Biomarkers: technologies and global markets, http://www.reportlinker.com/p0326190/Central-Nervous-System-CNS- Biomarkers-Technologies-and-Global-Markets.html.
63. P. Rolan, A.J. Atkinson Jr., and L.J. Lesko Use of biomarkers from drug discovery through clinical practice: report of the ninth european federation of pharmaceutical sciences conference on optimizing drug development Clin Pharmacol Ther 73 2003 284 291 (Pubitemid 36403588)
64. L.D. Jacobs, R.W. Beck, J.H. Simon, R.P. Kinkel, C.M. Brownscheidle, and T.J. Murray Intramuscular interferon beta-1α therapy initiated during a first demyelinating event in multiple sclerosis N Eng J Med 343 2000 898 904
65. M.J. Marino, L.J.S. Knutsen, and M. Williams Emerging opportunities for antipsychotic drug discovery in the postgenomic era J Med Chem 51 2008 1077 1107 (Pubitemid 351480372)
66. M. Williams Commentary genome-based CNS drug discovery: d-amino acid oxidase (DAAO) as a novel target for antipsychotic medications: progress and challenges Biochem Pharmacol 78 2009 1360 1365
67. E.J. Nestler, and S.E. Hyman Animal models of neuropsychiatric disorders Nat Neurosci 13 2010 1161 1179
68. X. Chen, G. Lee, B.S. Maher, A.H. Fanous, J. Chen, and The group investigators GWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia Mol Psychiatry 2010 10.1038/mp.2010.96
69. M.A. Benson, C.L. Tinsley, and D.J. Blake Myospryn is a novel binding partner for dysbindin in muscle J Biol Chem 279 2004 10450 10458 (Pubitemid 38372654)
70. K.S. Kendler Schizophrenia genetics and dysbindin: a corner turned? Am J Psychiatry 161 2004 1533 1536 (Pubitemid 39201447)
71. H. Nakagami, Y. Kikuchi, T. Katsuya, R. Morishita, H. Akasaka, and S. Saitoh Gene polymorphism of myospryn (cardiomyopathy-associated 5) is associated with left ventricular wall thickness in patients with hypertension Hypertens Res 30 2007 1239 1246 (Pubitemid 351176422)
72. M.B. First, and A. Tasman DSM-IV-TR mental disorders: diagnosis, etiology and treatment 2004 Wiley Chichester, UK
73. S.E. Hyman The diagnosis of mental disorders: the problem of reification Annu Rev Clin Psychol 6 2010 155 179
74. S.J. Enna, and M. Williams Challenges in the search for drugs to treat central nervous system disorders J Pharmacol Exp Ther 329 2009 404 411
75. T. Insel, B. Cuthbert, M. Garvey, R. Heinssen, D.S. Pine, and K. Quinn Research domain criteria (RDoC): toward a new classification framework for research on mental disorders Am J Psychiatry 167 2010 748 751
76. M. Day, F. Balci, H.I. Wan, G.B. Fox, J.L. Rutkowski, and G. Feuerstein Cognitive endpoints as disease biomarkers: optimizing the congruency of preclinical models to the clinic Curr Opin Invest Drugs 9 2008 696 707
77. A. Markou, C. Chiamulera, M.A. Geyer, M. Tricklebank, and T. Steckler Removing obstacles in neuroscience drug discovery: the future path for animal models Neuropsychopharmacol Rev 34 2009 74 89
78. H.W. Querfurth, and F.M. LaFerla Alzheimer's Disease N Engl J Med 362 2010 329 344
79. World Alzheimer report 2009 http://www.alz.org/national/documents/report- summary-2009worldalzheimerreport.pdf.
80. M.M.B. Breteler Mapping out biomarkers for Alzheimer disease J Am Med Assoc 305 2011 304 305
81. B. Dubois, H.H. Feldman, J. Jacova, J.L. Cummings, S.T. DeKosky, and P. Barberger-Gateau Revising the definition of Alzheimer's disease: a new lexicon Lancet Neurol 9 2010 1118 1122
82. H. Kaduszkiewicz, T. Zimmermann, H.-P. Beck-Bornholdt, and H. van den Bussche Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials Br Med J 331 2005 321
83. P. Raina, P. Santaguida, A. Ismaila, C. Patterson, D. Cowan, and M. Levine Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline Ann Intern Med 148 2008 379 397 (Pubitemid 351665469)
84. M. Citron Alzheimer's disease: strategies for disease modification Nat Rev Drug Discov 9 2010 387 398
85. M. Williams Progress in Alzheimer's disease drug discovery: an update Curr Opin Invest Drugs 10 2009 23 34
86. J.J. Palop, and L. Mucke Amyloid-β-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks Nat Neurosci 13 2010 812 818
87. R.J. Castellani, H.-G. Lee, X. Zhu, G. Perry, and M.A. Smith Alzheimer disease pathology as a host response J Neuropathol Exp Neurol 67 2008 523 531 (Pubitemid 351787079)
88. W.-Q. Zhao, F.G. De Felice, S. Fernandez, H. Chen, M.P. Lambert, and M.J. Quon Amyloid beta oligomers induce impairment of neuronal insulin receptors Fed Assoc Soc Exp Biol J 22 2008 246 260
89. P.I. Moreira, M.S. Santos, R. Seica, and C.R. Oliveria Brain mitochondrial dysfunction as a link between Alzheimer's disease and diabetes J Neurol Sci 257 2007 206 214 (Pubitemid 46856489)
90. P. Taupin Adult neurogenesis, neural stem cells and Alzheimer's disease: developments, limitations, problems and promises Curr Alzheimer Res 2009 461 470
91. T. Ma, C.A. Hoeffer, E. Capetillo-Zarate, F. Yu, H. Wong, and M.T. Lin Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease PLoS One 5 2010 e12845 10.1371/journal. pone.0012845
92. Y.S Eisele, U. Obermuller, G. Heilbronner, F. Baumann, S.A. Kaeser, and H. Wolburg Peripherally applied Aβ-containing inoculates induce cerebral β-amyloidosis Science 330 2010 980 982
93. J. Vaya, and H.M. Schipper Oxysterols, cholesterol homeostasis, and Alzheimer disease J Neurochem 102 2007 1727 1737 (Pubitemid 47329280)
94. L. Bertram, M.B. McQueen, K. Mullin, D. Blacker, and R.E. Tanzi Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database Nat Genet 39 2007 17 23 (Pubitemid 46026496)
95. Cure Alzheimer's Fund, http://www.curealzfund.org/spotlights/a-major- acheivement-the-alzheimers-genome-project. [Accessed 12/26/10].
96. T.M. Feulner, S.M. Laes, P. Friedrich, S. Wagenpfeil, S.H.R. Wurst, and C. Riehle Examination of the current top candidate genes for AD in a genome-wide association study Mol Psychiatry 15 2010 756 766
97. R.B. Nelson Back to the plaque: emerging studies that refocus attention on the neuritic plaque in Alzheimer's disease Ann Rev Med Chem 45 2010 315 328
98. H.-G. Lee, G. Perry, P.I. Moreira, M.R. Garrett, Q. Liu, and X. Zhu Tau phosphorylation in Alzheimer's disease: pathogen or protector? Trends Mol Med 11 2005 164 169
99. M.P. Mazanetz, and Fischer PM Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases Nat Rev Drug Discov 6 2007 464 479 (Pubitemid 47064569)
100. D.P. Hanger, B.H. Anderton, and W. Noble Tau phosphorylation: the therapeutic challenge for neurodegenerative disease Trends Mol Med 15 2009 112 119
101. K.R. Brunden, J.Q. Trojanowski, and V.M.Y. Lee Advances in tau-focused drug discovery for Alzheimer's disease and related tauopathies Nat Rev Drug Discov 8 2009 783 793
102. R.C. Green, L.S. Schnieder, D.A. Amato, A.P. Beelen, G. Wilcock, and E.A. Swabb Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease J Am Med Assoc 302 2009 2557 2564
103. J. Cummings What can be inferred from the interruption of the semagacestat trial for treatment of Alzheimer's disease? Biol Psychiatry 68 2010 876 878
104. M.N. Sabbagh, and C. Berk Latrepirdine for Alzheimer's disease: trials and tribulations Future Neurol 5 2010 645 665
105. D. Morgan Immunotherapy for Alzheimer's disease J Int Med 269 2011 54 63
106. F. Panza, V. Frisardi, B.P. Imbimbo, G. D'Onofrio, G. Pietrarossa, and A. Pilotto Bapineuzumab: anti-β-amyloid monoclonal antibodies for the treatment of Alzheimer's disease Immunotheraphy 2 2010 767 782
107. R.J. Castellani, H.-G. Lee, X. Zhu, A. Nunomura, G. Perry, and M.A. Smith Neuropathology of Alzheimer's disease: pathognomonic but not pathogenic Acta Neuropathol 111 2006 503 509 (Pubitemid 43778954)
108. G. Miller Alzheimer's biomarker initiative hits its stride Science 326 2009 386 389
109. R.S. Doody, V. Pavlik, P. Massman, S. Rountree, E. Darby, and W. Chan Predicting progression of Alzheimer's disease Alzheimer's Res Ther 2 2010 2
110. J.F. Benge, S. Balsis, L. Geraci, P.J. Massman, and R.S. Doofy How well do the ADAS-cog and its subscales measure cognitive dysfunction in alzheimer's disease? Demen Geriatr Cogn Disord 28 2009 63 69
111. A.J. Mitchell A meta-analysis of the accuracy of the mini-mental state examination in the detection of dementia and mild cognitive impairment J Psychiatr Res 43 2009 411 431
112. A.F. Fotenos, M.A. Mintun, A.Z. Snyder, J.C. Morris, and R.L. Buckner Brain volume decline in aging. Evidence for a relationship between socioeconomic status, preclinical Alzheimer Disease, and reserve Arch Neurol 65 2008 113 120
113. L. Mosconi, V. Berti, L. Glodzik, A. Pupi, S. De Santi, and M.J. de Leon Pre-clinical detection of Alzheimer's disease using FDG-PET, with or without amyloid imaging J Alzheimer Dis 20 2010 843 854
114. A. Kadir, O. Almkvisat, A. Forsberga, A. Wall, H. Eblere, and B. Lngström Dynamic changes in PET amyloid and FDG imaging at different stages of Alzheimer's disease Neurobiol Aging 2010 10.1016/j.neurobiolaging.2010.06015
115. 11C-PIB scans for diagnosing Alzheimer's disease J Nucl Med 49 2008 1262 1269
116. A. Forsberg, O. Almkvist, H. Engler, A. Wall, B. Langstrom, and A. Nordberg High PIB retention in Alzheimer's disease is an early event with complex relationship with csf biomarkers and functional parameters Curr Alzheimer Res 7 2010 56 61
117. C.M. Clark, J.A. Schneider, B.J. Bedell, T.G. Beach, W.B. Bilker, and M.A. Mintun Use of florbetapir-PET for imaging β-amyloid pathology J Am Med Assoc 305 2011 275 283
118. H. Hampel, R. Frank, K. Broich, S.J. Teipel, R.G. Katz, and J. Hardy Biomarkers for Alzheimer's disease: academic, industry, and regulatory perspectives Nat Rev Drug Discov 7 2010 560 574
119. E. Portelius, R.A. Dean, M.K. Gustavsson, U. Andreasson, and Zetterberg H A novel Aβ isoform pattern in CSF reflects γ-secretase inhibition in Alzheimer disease Alzheimer's Res Ther 2 2010 7
120. K. Blennow, H. Hampel, M. Weiner, and H. Zetterberg Cerebrospinal fluid and plasma biomarkers in Alzheimer disease Nat Rev Neurol 6 2010 131 144
121. Z. Zetterberg, N. Mattsson, K. Blennow, and B. Olsson Use of theragnostic markers to select drugs for phase II/III trials for Alzheimer disease Alzheimer's Res Ther 2 2010 32
122. H.J. Aizenstein, R.D. Nebes, J.A. Saxton, J.C. Price, A. Chester, and C.A. Mathis Frequent amyloid deposition without significant cognitive impairment among the elderly Arch Neurol 65 2008 1509 1517
123. M.E. Clementi, S. Mann, M. Coletta, F. Orsini, B. Giradina, and B. Misiti Aβ(31-35) and Aβ(25-35) fragments of amyloid beta-protein induce cellular death through apoptotic signals: Role of the redox state of methionine-35 FEBS Lett 579 2005 2913 2918 (Pubitemid 40725266)
124. G.A. Krafft, and W.L. Klein ADDLs and the signaling web that leads to Alzheimer's disease Neuropharmacology 59 2010 230 242
125. G.M. Shankar, S. Li, T.H. Mehta, A. Garcia-Munoz, N.E. Shepardson, and I. Smith Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory Nat Med 14 2008 837 842
126. S. Lesné, M.T. Koh, L. Kotilinek, R. Kayed, C.G. Glabe, and A. Yang A specific amyloid β-assembly in the brain impairs memory Nature 440 2006 352 357
127. L.M. Billings, K.N. Green, J.L. McGaugh, and F.M. LaFerla Learning decreases Aβ × 56 and tau pathology and ameliorates behavioral decline in 3 × Tg-AD mice J Neurosci 27 2007 751 761 (Pubitemid 46174493)
128. E. Portelius, E. Price, G. Brinkmalm, M. Stiteler, M. Olsson, and R. Persson A novel pathway for amyloid precursor protein processing Neurobiol Aging 2009 10.1016/j.neurobiolaging.2009.06.002
129. E Portelius, A. Westman-Brinkmalm, H. Zetterberg, and K. Blennow Determination of β-amyloid peptide signatures in cerebrospinal fluid using immunoprecipitation-mass spectrometry J Proteome Res 5 2006 1010 1016
130. K. Blennow, and H. Hampel CSF markers for incipient Alzheimer's disease Lancet Neurol 2 2003 605 613 (Pubitemid 37162569)
131. L.M. Shaw, H. Vanderstichele, M. Knapik-Czajka, C.M. Clark, P.S. Aisen, and R.C. Petersen Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative studies Ann Neurol 65 2009 403 413
132. C.R. Jack Jr., H.J. Wiste, P. Vemuri, S.D. Weigand, M.L. Senjem, and G. Zeng Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer's disease Brain 133 2010 3336 3348
133. 42 peptides in cerebrospinal fluid and prediction of progression of mild cognitive impairment Clin Chem 51 2005 1650 1660 (Pubitemid 41233100)
134. J. Wiltfang, H. Esselmann, A. Smirnov, M. Bibl, L. Cepek, and P. Steinacker β-amyloid peptides in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease Ann Neurol 54 2003 263 267 (Pubitemid 36909629)
135. M. Bibl, B. Mollenhauer, H. Esselmann, P. Lewczuk, H.-W. Klafki, and B. Sparbier CSF amyloid-β-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia Brain 129 2006 1177 1187
136. N.S. Schoonenboom, C. Mulder, G.J. Van Kamp, S.P. Mehta, P. Scheltens, and M.A. Blankenstein Amyloid β 38, 40, and 42 species in cerebrospinal fluid: more of the same? Ann Neurol 58 2005 139 142 (Pubitemid 40962469)
137. A. Siderowf, S.X. Xie, H. Hurtig, D. Weintraub, J. Duda, and A. Chen-Plotkin CSF amyloid β 1-42 predicts cognitive decline in Parkinson disease Neurology 75 2010 1055 1056
138. L.S. Schneider, R.E. Kennedy, and G.R. Cutter The Alzheimer's Disease Neuroimaging Initiative. Requiring an amyloid-β1-42 biomarker for prodromal Alzheimer's disease or mild cognitive impairment does not lead to more efficient clinical trials Alzheimer's Dementia 6 2010 e367 e377
139. H. Hampel, K. Blennow, L.M. Shaw, Y.C. Hoessler, H. Zetterberg, and J.Q. Trojanowski Total and phosphorylated tau protein as biological markers of Alzheimer's disease Exp Gerentol 45 2010 30 40
140. F. Hernandez, J. Avila, and Tauopathies Mol Life Sci 64 2007 2219 2233
141. D.P. Hanger, H.L. Byers, S. Wray, K.Y. Leung, M.J. Saxton, and A. Seereeram Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis J Biol Chem 282 2007 23645 23654 (Pubitemid 47311907)
142. K. Iqbal, F. Liu, C.-X. Gong, A.D. Alonso, and I. Grundke-Iqbal Mechanisms of tau-induced neurodegeneration Acta Neuopathol 118 2010 53 69
143. S.J. Greco, S. Sarkar, J.M. Johnston, and N. Tezapsidis Leptin regulates tau phosphorylation and amyloid through AMPK in neuronal cells Biochem Biophys Res Commun 380 2009 98 104
144. D.O. Azorsa, R.H. Robeson, D. Frost, B. Meec hoovet, G.R. Brautigam, and C. Dickey High-content siRNA screening of the kinome identifies kinases involved in Alzheimer's disease-related tau hyperphosphorylation Biomed Chromatogr Genomics 11 25 2010 http://www.biomedcentral.com/1471-2164/11/25
145. H. Bartosik-Psujek, and Z. Stelmasiak The CSF levels of total-tau and phosphotau in patients with relapsing-remitting multiple sclerosis J Neural Trans 113 2006 339 345 (Pubitemid 43201100)
146. N. Itoh, H. Arai, K. Urakami, K. Ishiguro, H. Ohno, and H. Hampel Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer's disease Ann Neurol 50 2001 150 156 (Pubitemid 32738138)
147. K. Buerger, R. Zinkowski, S.J. Teipel, T. Tapiola, H. Arai, and K. Blennow Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231 Arch Neurol 59 2002 1267 1272 (Pubitemid 34856379)
148. S. Engelborghs, K. De Vreese, T. Van de Casteele, H. Vanderstichele, B. Van Everbroeck, P. Cras, J.-J. Martin, E. Vanmechelen, and P.P. De Deyn Diagnostic performance of a CSF-biomarker panel in autopsy-confirmed dementia Neurobiol Aging 29 2008 1143 1159 (Pubitemid 351822410)
149. P. Lewczuk, H. Esselmann, M. Bibl, G. Beck, J.M. Maler, and M. Otto Tau protein phosphorylated at threonine 181 in CSF as a neurochemical biomarker in Alzheimer's disease. Original data and review of the literature J Mol Neurosci 23 2004 115 122 (Pubitemid 41359194)
150. H. Hampel, K. Buerger, R. Zinkowski, S.J. Teipel, A. Goernitz, and N. Andreasen Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheimer disease: a comparative cerebrospinal fluid study Arch Gen Psychiatry 61 2004 95 102 (Pubitemid 38044645)
151. A.M. Fagan, M.A. Mintun, A.R. Shah, P. Alde, and C.M. Roe Cerebrospinal fluid tau and ptau181 increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer's disease EMBO Mol Med 1 2009 371 380
152. O. Hansson, H. Zetterberg, P. Buchhave, E. Londos, K. Blennow, and L. Minthon Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study Lancet Neurol 5 2006 228 234 (Pubitemid 43238346)
153. N. Mattsson, H. Zetterberg, O. Hansson, N. Andreasen, L. Parnetti, and M. Jonsson CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment J Am Med Assoc 302 2009 385 393
154. J.S.K. Kauwe, J. Wang, K. Mayo, J.C. Morris, M. Anne, and A.M. Fagan Alzheimer's disease risk variants show association with cerebrospinal fluid amyloid beta Neurogenetics 10 2009 13 17
155. R. Mihaescu, S.B. Detmar, M.C. Cornel, W.M. van der Flier, P. Heutink, and E.M. Hol Translational research in genomics of Alzheimer's disease: a review of current practice and future perspectives J Alzheimer Dis 20 2010 967 980
156. S.O. Breno, Diniz, A. Jony, Pinto Jr., and Orestes Vicente Forlenz Do CSF total tau, phosphorylated tau, and b-amyloid 42 help to predict progression of mild cognitive impairment to Alzheimer's disease? A systematic review and meta-analysis of the literature World J Biol Psychiatry 9 2008 172 182
157. G. De Meyer, F. Shapiro, H. Vanderstichele, E. Vanmechelen, S. Engelborghs, and P.P. De Deyn For the Alzheimer's disease neuroimaging initiative. Diagnosis-independent Alzheimer disease biomarker signature in cognitively normal elderly people Arch Neurol 67 2010 949 956
158. P. Vemuri, H.J. Wiste, S.D. Weigand, D.S. Knopman, J.Q. Trojanowski, and L.M. Shaw Serial MRI and CSF biomarkers in normal aging, MCI, and AD Neurology 75 2010 143 151
159. W. Swardfager, K. Lanctot, L. Rothenburg, A. Wong, J. Cappell, and N. Hermann A met-analysis of cytokines in Alzheimer's disease Biol Psychiatry 68 2010 930 941
160. L. Olson, and C. Humpel Growth factors and cytokines/chemokines as surrogate biomarkers in cerebrospinal fluid and blood for diagnosing Alzheimer's disease and mild cognitive impairment Exp Gerentol 45 2010 41 46
161. A. Papassotiropoulos, M. Fountoulakis, T. Dunckley, D.A. Stephan, and E.M. Reiman Genetics, transcriptomics, and proteomics of Alzheimer's disease J Clin Psychiatry 67 2006 652 670 (Pubitemid 43764244)
162. M. Thambisetty, A. Simmons, L. Velayudhan, A. Hye, J. Campbell, and Y. Zhang Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease Arch Gen Psychiatry 67 2010 739 748
163. M.M. Reddy, R. Wilson, J. Wilson, S. Connell, A. Gocke, and L. Hynan Identification of candidate IgG biomarkers for Alzheimer's disease via combinatorial library screening Cell 144 2011 132 142
164. J. Zhang, D.R. Goodlett, J.F. Quinn, E. Peskind, J.A. Kaye, and Y. Zhou Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer disease J Alzheimers Dis 7 2005 125 133 (Pubitemid 40592186)
165. E.M. Castano, A.E. Roher, C.L. Esh, T.A. Kokjohn, and T. Beach Comparative proteomics of cerebrospinal fluid in neuropathologically-confirmed Alzheimer's disease and non-demented elderly subjects Neurol Res 28 2006 155 163
166. E.J. Finehout, Z. Franck, L.H. Choe, N. Relkin, and K.H. Lee Cerebrospinal fluid proteomic biomarkers for Alzheimer's disease Ann Neurol 61 2007 120 129 (Pubitemid 46363839)
167. C.L. Maarouf, T.M. Andacht, T.A. Kokjohn, E.M. Castaño, L.I. Sue, and T.G. Beach Proteomic analysis of Alzheimer's disease cerebrospinal fluid from neuropathologically diagnosed subjects Curr Alzheimer Res 6 2009 399 406
168. Y.S. Choi, L.H. Choe, and K.H. Lee Recent cerebrospinal fluid biomarker studies of Alzheimer's disease Exp Rev Proteome 7 2010 919 929
169. Sakoglu Ü, Upadhyay J, Chin C-L, Chandran P, Baker et al., Paradigm Shift in Translational Neuroimaging of CNS Disorders. Biochem Pharmacol, this issue, doi:10.1016/j.bcp.2010.12.029.
170. S.W. Pimplikar Alzheimer's isn't up to the tests 2010 New York Times http://www.nytimes.com/2010/07/20/opinion/20pimplikar.html?-r=1&pagewanted= print. [July 19].
171. G. Kolata Tests detect Alzheimer's risks, but should patients be told? December 17 2010 New York Times
172. J.C. Dooren FDA skeptical about detecting Alzheimer's Wall St. J January 2011 D2
173. G.F.D.A. Kolata Sees promise in Alzheimer's imaging drug 2011 New York Times http://www.nytimes.com/2011/01/21/health/21alzheimers.html?-r=1&nl= todaysheadlines&emc=tha2 [January 21]
174. J.C. Dooren Panel seeks data on drug for Alzheimer's Scanning Wall St. J January 2011 B4
175. E. Holmes, T.M. Tsang, J.T.J. Huang, F.M. Leweke, and Koethe D Metabolic profiling of CSF: evidence that early intervention may impact on disease progression and outcome in schizophrenia PLoS Med 3 2006 e327
176. E. Schwarz, and S. Bahn Cerebrospinal fluid: identification of diagnostic markers for schizophrenia Exp Rev Mol Diagn 8 2008 209 216 (Pubitemid 351469440)
177. E.J. Davies Developmental aspects of schizophrenia and related disorders: possible implications for treatment strategies Adv Psychiatr Treat 13 2007 384 391 (Pubitemid 351148899)
178. J.L. Stanta, R. Saldova, W.B. Struwe, J.C. Byrne, F.M. Leweke, and M. Rothermund Identification of N-glycosylation changes in the CSF and serum in patients with schizophrenia J Proteome Res 9 2010 4476 4489
179. P. Gudmundsson, I. Skoog, M. Waern, K. Blennow, S. Pálsson, and L. Rosengren The relationship between cerebrospinal fluid biomarkers and depression in elderly Am J Geriatr Psychiatry 15 2007 832 838
180. M. Colaianna, P.M. Tucci, M. Zotti, M.G. Morgese, and S. Schiavone Soluble bamyloid1-42: a critical player in producing behavioural and biochemical changes evoking depressive-related state Br J Pharmacol 159 2010 1704 1715
181. N. Pomara, and J.J. Sidtis Brain neurotoxic amyloid-beta peptides: their potential role in the pathophysiology of depression and as molecular therapeutic targets Br J Pharmacol 161 2010 768 770
182. K. Marek, D. Jennings, G. Tamagnan, and J. Seibyl Biomarkers for Parkinson's disease: tools to assess Parkinson's disease onset and progression Ann Neurol 64 Suppl. 2008 S111 S121
183. M. Frasier, S. Chowdhury, J. Eberling, and T. Sherer Biomarkers in Parkinson's disease: a funder's perspective Biomarkers Med 4 2010 723 729
184. M. Shi, W.M. Caudle, and J. Zhang Biomarker discovery in neurodegenerative disease: a proteomic approach Neurobiol Dis 35 2009 157 164
185. K.D. van Dijk, C.E. Teunissen, B. Drukarch, C.R. Jimenez, H.J. Groenewegen, and H.W. Berendse Diagnostic cerebrospinal fluid biomarkers for Parkinson's disease: a pathogenetically based approach Neurobiol Dis 39 2010 229 241
186. T. Tokuda, S.A. Salem, D. Allsop, T. Mizuno, M. Nakagawa, and M.M. Qureshi Decreased a-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease Biochem Biphys Res Commun 349 2006 162 166 (Pubitemid 44331776)
187. H. Tumani, H.P. Hartung, B. Hemmer, C. Teunissen, F. Deisenhammer, and G. Giovannoni Cerebrospinal fluid biomarkers in multiple sclerosis Neurobiol Dis 35 2009 117 127
188. M. Tintore, A. Rovira, J. Rio, C. Tur, R. Pelayo, and C. Nos Do oligoclonal bands add information to MRI in first attacks in multiple sclerosis Neurology 25 2008 1079 1083 (Pubitemid 351464763)
189. M.P. Stoop, V. Singh, L.J. Dekker, M.K. Titulaer, C. Stingl, and P.C. Burgers Proteomics comparison of cerebrospinal fluid of relapsing remitting and primary progressive multiple sclerosis PLoS ONE 5 2010 e12442
190. M.J. Millan The discovery and development of pharmacotherapy for psychiatric disorders: a critical survey of animal and translational models and perspectives for their improvement R.A. McArthur, F. Borsini, Animal and translational models for CNS drug discovery. Vol. 1 2008 Academic Press Burlington, MA 1 57
191. M. Lindner Clinical attrition due to biased preclinical assessments of potential efficacy Pharmacol Ther 115 2007 148 175 (Pubitemid 46992811)
192. D.F. Klein The loss of serendipity in psychopharmacology J Am Med Assoc 299 2008 1063 1065 (Pubitemid 351347065)
193. B.L. Roth, D.G. Sheffler, and W.K. Kroeze Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia Nat Rev Drug Discov 3 2004 353 359 (Pubitemid 38499762)
194. M.J. Owens, W.N. Morgan, S.J. Plott, and C.B. Nemeroff Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites J Pharmacol Exp Ther 283 1997 1305 1322 (Pubitemid 28016506)
195. Danish University Antidepressant Group Citalopram: clinical effect profile in comparison with clomipramine. A controlled multicenter study J Psychopharmacol 90 1986 131 138
196. Danish University Antidepressant Group Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study J Affect Disord 18 1990 289 299
197. I.M. Anderson Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability J Affect Disord 58 2000 19 36 (Pubitemid 30173208)
198. J.W. Williams Jr., C.D. Mulrow, E. Chiquette, P.H. Hitchcock-Noel, C. Aguilar, and J. Cornell A systematic review of newer pharmacotherapies for depression in adults: evidence report summary: clinical guidelines, part 2 Ann Intern Med 132 2000 743 775
199. D. Eyding, M. Lelgemann, U. Grouven, M. Harter, M. Kromp, and T. Kaiser Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials Br Med J 341 2010 c4737
200. M. Wehling Assessing the translatability of drug projects: what needs to be scored to predict success? Nat Rev Drug Discov 8 2009 541 546
201. D.F. Horrobin Modern biomedical research: an internally self-consistent universe with little contact with medical reality? Nat Rev Drug Discov 2 2003 151 154 (Pubitemid 37361647)
202. A.A. Nierenberg The perfect storm: CNS drug development in trouble CNS Spectr 15 2010 282 283