Biomarker identification for diagnosis of Alzheimer's disease

Expert Opinion on Medical Diagnostics

Volumn 2, Issue 5, 2008, Pages 577-591

  Pelech, Steven ^a,b  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b Kinexus Bioinformatics Corporation   (Canada)

Author keywords

Alzheimer's disease; Amyloid beta; Amyotropic lateral sclerosis; Biomarker; Diagnosis; Frontal temporal dementia; Tau

Indexed keywords

ALPHA SYNUCLEIN; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; AMYLOID PRECURSOR PROTEIN; BINDING PROTEIN; BIOLOGICAL MARKER; CALCINEURIN; COLLAPSIN RESPONSE MEDIATOR PROTEIN 2; CYCLIN DEPENDENT KINASE 5; CYTOKINE; ELONGATION FACTOR 2; EUKARYOTE INITIATION FACTOR 4E BINDING PROTEIN 1; GLIAL FIBRILLARY ACIDIC PROTEIN; GLYCOGEN SYNTHASE KINASE 3; INITIATION FACTOR 2; INITIATION FACTOR 2ALPHA; INITIATION FACTOR 4E; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE P38; PROTEIN C JUN; PROTEIN KINASE B; PROTEIN KINASE R; PROTEIN P27; RAF PROTEIN; RETINOBLASTOMA PROTEIN; S6 KINASE; STRESS ACTIVATED PROTEIN KINASE; STRESS ACTIVATED PROTEIN KINASE 1; TAU PROTEIN; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; BLOOD SAMPLING; BRAIN BIOPSY; CEREBROSPINAL FLUID; GENE EXPRESSION; HUMAN; MONOCYTE; NONHUMAN; NUCLEOTIDE SEQUENCE; PATHOLOGY; PERIPHERAL BLOOD MONONUCLEAR CELL; PLASMA; PROTEIN ANALYSIS; PROTEIN PHOSPHORYLATION; PROTEOMICS; REVIEW;

EID: 77953366733     PISSN: 17530059     EISSN: 17530067     Source Type: Journal    
DOI: 10.1517/17530059.2.5.577     Document Type: Review

References (159)

1. Li Y, Nowotny P, Holmans P, et al. Association of late-onset Alzheimer's disease with genetic variation in multiple members of the GAPD gene family. Proc Natl Acad Sci USA 2004;101:15688-15693 (Pubitemid 39473549)
2. Kim SI, Voshol H, van Oostrum J, et al. Neuroproteomics: expression profiling of the brain's proteomes in health and disease. Neurochem Res 2004;29:1317-1331 (Pubitemid 39023504)
3. D'Ascenzo M, Relkin NR, Lee KH. Alzheimer's disease cerebrospinal fluid biomarker discovery: a proteomics approach. Curr Opin Mol Ther 2005;7:557-664 (Pubitemid 41763995)
4. Galasko D. Biomarkers for Alzheimer's disease - clinical needs and application. J Alzheimers Dis 2005;8:339-346
5. Zhang J, Goodlett DR, Montine TJ. Proteomic biomarker discovery in cerebrospinal fluid for neurodegenerative diseases. J Alzheimers Dis 2005;8:377-386
6. Cruts M, van Duijn CM, Backhovens H, et al. Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease. Hum Mol Genet 1998;7:43-51 (Pubitemid 28040736)
7. De Strooper B. Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO Reports 2007;8:141-146
8. Shen J, Kelleher RJ III. The presenilin hypothesis of Alzheimer's disease: Evidence for a loss-of-function pathogenic mechanism. Proc Natl Acad Sci USA 2007;104:403-409 (Pubitemid 46123039)
9. Hutton M. Presenilin mutations associated with fronto-temporal dementia. Ann Neurol 2004;55:604-606 (Pubitemid 38544319)
10. Wang JZ, Grundke-Iqbal I, Iqbal K. Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration. Eur J Neurosci 2007;25:59-68 (Pubitemid 46098893)
11. Grundke-Iqbal I, Iqbal K, Tung YC, et al. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 1986;83:4913-4917 (Pubitemid 16075509)
12. Mi K, Johnson GV. The role of tau phosphorylation in the pathogenesis of Alzheimer's disease. Curr Alzheimer Res 2006;3(5):449-463 (Pubitemid 46070114)
13. Pevalova M, Filipeik P, Novak M, et al. Post-translational modifications of tau protein. Bratisl Lek Listy 2006;107:346-353
14. Ferrer I, Barrachina M, Puig B, et al. Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol Dis 2005;20:392-400 (Pubitemid 41476265)
15. Strong MJ, Yang W, Strong WL, et al. Tau protein hyperphosphorylation in sporadic ALS with cognitive impairment. Neurology 2006;66:1770-1771 (Pubitemid 43964644)
16. Mawal-Dewan M, Schmidt ML, Balin B, et al. Identification of phosphorylation sites in PHF-TAU from patients with Guam amyotrophic lateral sclerosis/Parkinsonism-dementia complex. J Neuropathol Exp Neurol 1996;55:1051-1059 (Pubitemid 26338017)
17. Bussiere T, Hof PR, Mailliot C, et al. Phosphorylated serine422 on tau proteins is a pathological epitope found in several diseases with neurofibrillary degeneration. Acta Neuropathology (Berlin) 1999;97:221-230 (Pubitemid 29137270)
18. Schmidt ML, Huang R, Martin JA, et al. Neurofibrillary tangles in progressive supranuclear palsy contain the same tau epitopes identified in Alzheimer's disease PHFtau. J Neuropathol Exp Neurol 1996;55:534-539 (Pubitemid 26140836)
19. Vincent I, Jicha G, Rosado M, Dickson DW. Aberrant expression of mitotic cdc2/cyclin B1 kinase in degenerating neurons of Alzheimer's disease brain. J Neurosci 1997;17:3588-3598 (Pubitemid 27200586)
20. Hamdane M, Sambo AV, Delobel P, et al. Mitotic-like tau phosphorylation by p25-Cdk5 kinase complex. J Biol Chem 2003;278:34026-34034 (Pubitemid 37553239)
21. Woods YL, Cohen P, Becker W, et al. The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bepsilon at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase. Biochem J 2001;355:609-615 (Pubitemid 32434076)
22. Ferrer I. Differential expression of phosphorylated translation initiation factor 2 alpha in Alzheimer's disease and Creutzfeldt-Jakob's disease. Neuropathol Appl Neurobiol 2002;28:441-451 (Pubitemid 35425597)
23. Mandelkow EM, Thies E, Trinczek B, et al. MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons. J Cell Biol 2004;167:99-110 (Pubitemid 39363418)
24. Takahashi M, Uchikado H, Caprotti D, et al. Identification of G-protein coupled receptor kinase 2 in paired helical filaments and neurofibrillary tangles. J Neuropathol Exp Neurol 2006;65:1157-1169 (Pubitemid 44885940)
25. Herskovits AZ, Davies P. The regulation of tau phosphorylation by PCTAIRE 3: implications for the pathogenesis of Alzheimer's disease. Neurobiol Dis 2006;23:398-408 (Pubitemid 44109668)
26. Kawamata T, Taniguchi T, Mukai H, et al. A protein kinase, PKN, accumulates in Alzheimer neurofibrillary tangles and associated endoplasmic reticulum-derived vesicles and phosphorylates tau protein. J Neurosci 1998;18:7402-7410 (Pubitemid 28425824)
27. Pei JJ, Braak E, Braak H, et al. Localization of active forms of c-Jun kinase (JNK) and p38 kinase in Alzheimer's disease brains at different stages of neurofibrillary degeneration. J Alzheimers Dis 2001;3:41-48 (Pubitemid 32238249)
28. Zhu X, Raina AK, Rottkamp CA, et al. Activation and redistribution of c-jun N-terminal kinase/stress activated protein kinase in degenerating neurons in Alzheimer's disease. J Neurochem 2001;76:435-441 (Pubitemid 32097021)
29. Zhu X, Lee HG, Raina AK, et al. The role of mitogen-activated protein kinase pathways in Alzheimer's disease. Neurosignals 2002;11:270-281 (Pubitemid 37494394)
30. Liu F, Su Y, Li B, et al. Gonzalez-DeWhitt P, May PC, Ni B. Regulation of amyloid precursor protein (APP) phosphorylation and processing by p35/Cdk5 and p25/Cdk5. FEBS Lett 2003;547:193-196
31. Swatton JE, Sellers LA, Faull RL, et al. Increased MAP kinase activity in Alzheimer's and Down syndrome but not in schizophrenia human brain. Eur J Neurosci 2004;19:2711-2719 (Pubitemid 38746388)
32. Kim HS, Kim EM, Lee JP, et al. C-terminal fragments of amyloid precursor protein exert neurotoxicity by inducing glycogen synthase kinase-3beta expression. FASEB J 2003;17:1951-1953
33. Otth C, Concha II, Arendt T, et al. AbetaPP induces cdk5-dependent tau hyperphosphorylation in transgenic mice Tg2576. J Alzheimers Dis 2002;4:417-430 (Pubitemid 35397807)
34. Peel AL, Sorscher N, Kim JY, et al. Tau phosphorylation in Alzheimer's disease: potential involvement of an APP-MAP kinase complex. Neuromolecular Med 2004;5:205-218 (Pubitemid 40125302)
35. Pei JJ, Gong CX, An WL, et al. Okadaic-acid-induced inhibition of protein phosphatase 2A produces activation of mitogen-activated protein kinases ERK1/2, MEK1/2, and p70 S6, similar to that in Alzheimer's disease. Am J Pathology 2003;163:845-858 (Pubitemid 37040121)
36. Tian Q, Wang J. Role of serine/threonine protein phosphatase in Alzheimer's disease. Neurosignals 2002;11:262-269 (Pubitemid 37494393)
37. Liu F, Iqbal K, Grundke-Iqbal I, et al. Dephosphorylation of tau by protein phosphatase 5. J Biol Chem 2005;280:1790-1796
38. Vogelsberg-Ragaglia V, Schuck T, Trojanowski JQ, Lee VM. PP2A mRNA expression is quantitatively decreased in Alzheimer's disease hippocampus. Exp Neurol 2001;168:402-412 (Pubitemid 32289776)
39. Tanimukai H, Grundke-Iqbal I, Iqbal K. Up-regulation of inhibitors of protein phosphatase-2A in Alzheimer's disease. Am J Pathology 2005;166:1761-1771 (Pubitemid 40734399)
40. Cook CN, Hejna MJ, Magnuson DJ, Lee JM. Expression of calcipressin1, an inhibitor of the phosphatase calcineurin, is altered with aging and Alzheimer's disease. J Alzheimers Dis 2005;8:63-73 (Pubitemid 41267325)
41. Pei JJ, Sersen E, Iqbal K, Grundke-Iqbal I. Expression of protein phosphatases (PP-1, PP-2A, PP-2B and PTP-1B) and protein kinases (MAP kinase and P34cdc2) in the hippocampus of patients with Alzheimer disease and normal aged individuals. Brain Res 1994;655:70-76 (Pubitemid 24262993)
42. Wang YP, Wei ZL, Wang XC, et al. Comparative study of the expression and phosphorylation of neurofilament proteins of brain gray matter in Alzheimer's disease. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2001;23:445-449
43. Amada N, Aihara K, Ravid R, Horie M. Reduction of NR1 and phosphorylated Ca2+/calmodulin-dependent protein kinase II levels in Alzheimer's disease. Neuroreport 2005;16:1809-1813 (Pubitemid 41547052)
44. Wang YJ, Chen GH, Hu XY, et al. The expression of calcium/calmodulin- dependent protein kinase II-alpha in the hippocampus of patients with Alzheimer's disease and its links with AD-related pathology. Brain Res 2005;1031:101-118
45. Muyllaert D, Terwel D, Borghgraef P, et al. Transgenic mouse models for Alzheimer's disease: the role of GSK-3B in combined amyloid and tau-pathology. Rev Neurol (Paris ) 2006;162:903-977 (Pubitemid 44495481)
46. Taniguchi T, Doe N, Matsuyama S, et al. Transgenic mice expressing mutant (N279K) human tau show mutation dependent cognitive deficits without neurofibrillary tangle formation. FEBS Lett 2005;579:5704-5712 (Pubitemid 41460490)
47. Rosso SM, van Herpen E, Pijnenburg YA, et al. Total tau and phosphorylated tau 181 levels in the cerebrospinal fluid of patients with frontotemporal dementia due to P301L and G272V tau mutations. Arch Neurol 2003;60:1209-1213 (Pubitemid 37099625)
48. Lee HG, Perry G, Moreira PI, et al. Tau phosphorylation in Alzheimer's disease: pathogen or protector? Trends Mol Med 2005;11:164-169
49. Zhu X, Sun Z, Lee HG, et al. Distribution, levels, and activation of MEK1 in Alzheimer's disease. J Neurochem 2003;86:136-142 (Pubitemid 36753854)
50. Lagalwar S, Guillozet-Bongaarts AL, Berry RW, Binder LI. Formation of phospho-SAPK/JNK granules in the hippocampus is an early event in Alzheimer disease. J Neuropathol Exp Neurol 2006;65:455-464 (Pubitemid 44297267)
51. Pei JJ, Braak H, An WL, et al. Up-regulation of mitogen-activated protein kinases ERK1/2 and MEK1/2 is associated with the progression of neurofibrillary degeneration in Alzheimer's disease. Brain Res Mol Brain Res 2002;109:45-55
52. Sun A, Liu M, Nguyen XV, Bing G. p38 MAP kinase is activated at early stages in Alzheimer's disease brain. Exp Neurol 2003;183:394-405 (Pubitemid 37205081)
53. Thakur A, Wang X, Siedlak SL, et al. c-Jun phosphorylation in Alzheimer disease. J Neurosci Res 2007;85:1668-1673 (Pubitemid 46849614)
54. Sahara N, Vega IE, Ishizawa T, et al. Phosphorylated p38MAPK specific antibodies cross-react with sarkosyl-insoluble hyperphosphorylated tau proteins. J Neurochem 2004;90:829-838 (Pubitemid 39099964)
55. Webber KM, Smith MA, Lee HG, et al. Mitogen-and stress-activated protein kinase 1: convergence of the ERK and p38 pathways in Alzheimer's disease. J Neurosci Res 2005;79:554-560 (Pubitemid 40283355)
56. Li X, An WL, Alafuzoff I, et al. Phosphorylated eukaryotic translation factor 4E is elevated in Alzheimer brain. Neuroreport 2004;15:2237-2240
57. Pei JJ, Khatoon S, An WL, et al. Role of protein kinase B in Alzheimer's neurofibrillary pathology. Acta Neuropathology (Berlin) 2003;105:381-392
58. Griffin RJ, Moloney A, Kelliher M, et al. Activation of Akt/PKB, increased phosphorylation of Akt substrates and loss and altered distribution of Akt and PTEN are features of Alzheimer's disease pathology. J Neurochem 2005;93:105-117 (Pubitemid 40463520)
59. Ishii T, Furuoka H, Muroi Y, Nishimura M. Inactivation of integrin-linked kinase induces aberrant tau phosphorylation via sustained activation of glycogen synthase kinase 3beta in N1E-115 neuroblastoma cells. J Biol Chem 2003;278:26970-26975 (Pubitemid 36876850)
60. Leroy K, Boutajangout A, Authelet M, et al. The active form of glycogen synthase kinase-3beta is associated with granulovacuolar degeneration in neurons in Alzheimer's disease. Acta Neuropathol (Berl ) 2002;103:91-99 (Pubitemid 36067485)
61. Pei JJ, Tanaka T, Tung YC, et al. Distribution, levels, and activity of glycogen synthase kinase-3 in the Alzheimer disease brain. J Neuropathol Exp Neurol 1997;56:70-78 (Pubitemid 127470328)
62. Mateo I, Infante J, Llorca J, et al. Association between glycogen synthase kinase-3beta genetic polymorphism and late-onset alzheimer's disease. Dement Geriatr Cogn Disord 2006;21:228-232
63. Rockenstein E, Torrance M, Adame A, et al. Neuroprotective effects of regulators of the glycogen synthase kinase-3beta signaling pathway in a transgenic model of Alzheimer's disease are associated with reduced amyloid precursor protein phosphorylation. J Neurosci 2007;27:1981-1991 (Pubitemid 46310321)
64. Noble W, Planel E, Zehr C, et al. Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo. Proc Natl Acad Sci USA 2005;102:6990-6995 (Pubitemid 40675429)
65. Vijayan S, El-Akkad E, Grundke-Iqbal I, Iqbal K. A pool of beta-tubulin is hyperphosphorylated at serine residues in Alzheimer disease brain. FEBS Lett 2001;509:375-381 (Pubitemid 34031964)
66. An WL, Cowburn RF, Li L, et al. Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer's disease. Am J Pathol 2003;163:591-607 (Pubitemid 36909421)
67. Liao L, Cheng D, Wang J, et al. Proteomic characterization of postmortem amyloid plaques isolated by laser capture microdissection. J Biol Chem 2004;279:37061-8 • A careful identification of about 488 proteins in AD plaques.
68. Chang RC, Wong AK, Ng HK, Hugon J. Phosphorylation of eukaryotic initiation factor-2alpha (eIF2alpha) is associated with neuronal degeneration in Alzheimer's disease. Neuroreport 2002;13:2429-2432 (Pubitemid 36143538)
69. Korolainen MA, Auriola S, Nyman TA, et al. Proteomic analysis of glial fibrillary acidic protein in Alzheimer's disease and aging brain. Neurobiol Dis 2005;20:858-870 (Pubitemid 41619361)
70. Lee HG, Ueda M, Zhu X, et al. Ectopic expression of phospho-Smad2 in Alzheimer's disease: uncoupling of the transforming growth factor-beta pathway? J Neurosci Res 2006;84:1856-1861
71. Ueberham U, Ueberham E, Gruschka H, Arendt T. Altered subcellular location of phosphorylated Smads in Alzheimer's disease. Eur J Neurosci 2006;24:2327-2334 (Pubitemid 44622353)
72. Andreasen N, Minthon L, Davidsson P, et al. Evaluation of CSF-tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice. Arch Neurol 2001;58:349-50 •• A study with 241 subjects for predicting development of AD with CSF. (Pubitemid 32217453)
73. Andreasen N, Vanmechelen E, Vanderstichele H, et al. Cerebrospinal fluid levels of total-tau, phospho-tau and A beta 42 predicts development of Alzheimer's disease in patients with mild cognitive impairment. Acta Neurol Scand Suppl 2003;179:47-51 • A study with 76 subjects for predicting development of AD with CSF.
74. Itoh N, Arai H, Urakami K, et al. Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer's disease. Ann Neurol 2001;50:150-6 •• A study with 570 subjects for predicting development of AD with CSF. (Pubitemid 32738138)
75. Urakami K, Ito N, Arai H, et al. The measurement of phosphorylated tau in human cerebrospinal fluid as a diagnostic marker for Alzheimer's disease. Seishin Shinkeigaku Zasshi 2003;105:393-397
76. Holmberg B, Johnels B, Blennow K, Rosengren L. Cerebrospinal fluid Abeta42 is reduced in multiple system atrophy but normal in Parkinson's disease and progressive supranuclear palsy. Movement Disorders 2003;18:186-190 (Pubitemid 36305463)
77. Pirttila T, Schapiro MB, Rapoport SI, et al. Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231. Arch Neurol 2002;59:1267-1272 (Pubitemid 34856379)
78. de Leon MJ, DeSanti S, Zinkowski R, et al. MRI and CSF studies in the early diagnosis of Alzheimer's disease. J Intern Med 2004;256:205-223 (Pubitemid 39222990)
79. Ishiguro K, Ohno H, Arai H, et al. Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease. Neuroscience Lett 1999;270:91-94 (Pubitemid 29333843)
80. Hu Y, He S, Wang J. Diagnostic value of tau in cerebrospinal fluid in Alzheimer disease. Zhonghua Yi Xue Za Zhi 2001;81:1377-1379
81. Blennow K, Vanmechelen E, Hampel H. CSF total tau, Abeta42 and phosphorylated tau protein as biomarkers for Alzheimer's disease. Molecular Neurobiol 2001;24:87-97
82. Fellgiebel A, Siessmeier T, Scheurich A, et al. Association of elevated phospho-tau levels with Alzheimer-typical 18F-fluoro-2-deoxy-D-glucose positron emission tomography findings in patients with mild cognitive impairment. Biology Psychiatry 2004;56:279-283 (Pubitemid 39092943)
83. Nagga K, Gottfries J, Blennow K, Marcusson J. Cerebrospinal fluid phospho-tau, total tau and beta-amyloid(1-42) in the differentiation between Alzheimer's disease and vascular dementia. Dementia Geriatric Cognition Disorders 2002;14:183-190
84. Hu YY, He SS, Wang X, et al. Levels of nonphosphorylated and phosphorylated tau in cerebrospinal fluid of Alzheimer's disease patients. Am J Pathol 2002;160:1269-78 • A study with 191 subjects for predicting development of AD with CSF.
85. Mitchell A, Brindle N. CSF phosphorylated tau-does it constitute an accurate biological test for Alzheimer's disease? IInt J Geriatr Psychiatry 2003;18:407-411
86. Schonknecht P, Pantel J, Hunt A, et al. Levels of total tau and tau protein phosphorylated at threonine 181 in patients with incipient and manifest Alzheimer's disease. Neuroscience Lett 2003;339:172-174 (Pubitemid 36254803)
87. Olsson A, Vanderstichele H, Andreasen N, et al. Simultaneous measurement of beta-amyloid(1-42), total tau, and phosphorylated tau (Thr181) in cerebrospinal fluid by the xMAP technology. Clin Chem 2005;51:336-345
88. Lewczuk P, Esselmann H, Bibl M, et al. 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 2004;23:115-122 (Pubitemid 41359194)
89. Hansson O, Zetterberg H, Buchhave P, et al. Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 2006;5:228-34 • A large-scale study with 180 subjects. 90. Buerger K, Ewers M, Pirttila T, et al. CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease. Brain 2006;129:3035-3041 (Pubitemid 43238346)
90. Kapaki EN, Paraskevas GP, Tzerakis NG, et al. Cerebrospinal fluid tau, phospho-tau181 and beta-amyloid1-42 in idiopathic normal pressure hydrocephalus: a discrimination from Alzheimer's disease. Eur J Neurol 2007;14:168-173 (Pubitemid 46148304)
91. Buerger K, Zinkowski R, Teipel SJ, et al. Differentiation of geriatric major depression from Alzheimer's disease with CSF tau protein phosphorylated at threonine 231. Am J Psychiatry 2003;160:376-379 (Pubitemid 41110469)
92. Hampel H, Buerger K, Kohnken R, et al. Tracking of Alzheimer's disease progression with cerebrospinal fluid tau protein phosphorylated at threonine 231. Annals Neurol 2001;49:545-546 (Pubitemid 32281345)
93. Buerger K, Teipel SJ, Zinkowski R, et al. CSF tau protein phosphorylated at threonine 231 correlates with cognitive decline in MCI subjects. Neurology 2002;59:627-629 (Pubitemid 34920005)
94. Buerger K, Zinkowski R, Teipel SJ, et al. Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231. Arch Neurol 2002;59:1267-1272 (Pubitemid 34856379)
95. Hampel H, Burger K, Pruessner JC, et al. Correlation of cerebrospinal fluid levels of tau protein phosphorylated at threonine 231 with rates of hippocampal atrophy in Alzheimer disease. Arch Neurol 2005;62:770-773 (Pubitemid 40656092)
96. Schonknecht P, Hempel A, Hunt A, et al. Cerebrospinal fluid tau protein levels in schizophrenia. Eur Arch Psych Clin Neurosci 2003;253:100-102 (Pubitemid 37205485)
97. de Jong D, Jansen RW, Kremer BP, Verbeek MM. Cerebrospinal fluid amyloid beta42/phosphorylated tau ratio discriminates between Alzheimer's disease and vascular dementia. J Gerontol A Biol Sci Med Sci 2006;61:755-758 (Pubitemid 44148364)
98. Hesse C, Rosengren L, Andreasen N, et al. Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke. Neurosci Lett 2001;297:187-190 (Pubitemid 32011305)
99. Hu YY, He SS, Wang XC, et al. Elevated levels of phosphorylated neurofilament proteins in cerebrospinal fluid of Alzheimer disease patients. Neurosci Lett 2002;320:156-160 (Pubitemid 34164438)
100. Mollenhauer B, Bibl M, Wiltfang J, et al. Total tau protein, phosphorylated tau (181p) protein, beta-amyloid(1-42), and beta-amyloid(1-40) in cerebrospinal fluid of patients with dementia with Lewy bodies. Clin Chem Lab Med 2006;44:192-195
101. Blennow K, Vanmechelen E. Combination of the different biological markers for increasing specificity of in vivo Alzheimer's testing (Review). J Neural Transm Suppl 1998;53:223-235 (Pubitemid 28361783)
102. Formichi P, Battisti C, Radi E, Federico A. Cerebrospinal fluid tau, A beta, and phosphorylated tau protein for the diagnosis of Alzheimer's disease. J Cell Physiol 2006;208:39-46 (Pubitemid 43848987)
103. Sjogren M, Andreasen N, Blennow K. Advances in the detection of Alzheimer's disease-use of cerebrospinal fluid biomarkers (Review). Clin Chim Acta 2003;332:1-10 (Pubitemid 36577482)
104. Wiltfang J, Lewczuk P, Riederer P, et al. Consensus paper of the WFSBP Task Force on Biological Markers of Dementia: the role of CSF and blood analysis in the early and differential diagnosis of dementia. World J Biol Psychiatry 2005;6:69-84 (Pubitemid 40895131)
105. Maccioni RB, Lavados M, Guillon M, et al. Anomalously phosphorylated tau and Abeta fragments in the CSF correlates with cognitive impairment in MCI subjects. Neurobiol Aging 2006;27:237-244 (Pubitemid 43038547)
106. Buerger K, Otto M, Teipel SJ, et al. Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt-Jakob disease. Neurobiol Aging 2006;27:10-15 (Pubitemid 41627944)
107. Brew BJ, Pemberton L, Blennow K, et al. CSF amyloid beta42 and tau levels correlate with AIDS dementia complex. Neurology 2005;65:1490-1492 (Pubitemid 41552790)
108. Abdi F, Quinn JF, Jankovic J, et al. Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders. J Alzheimers Dis 2006;9:293-348 •• Over 1500 CSF proteins were identified and 136 were uniquely altered in AD.
109. Puchades M, Hansson SF, Nilsson CL, et al. Proteomic studies of potential cerebrospinal fluid protein markers for Alzheimer's disease. Brain Res Mol Brain Res 2003;118:140-146 (Pubitemid 37238996)
110. Finehout EJ, Franck Z, Choe LH, et al. Cerebrospinal fluid proteomic biomarkers for Alzheimer's disease. Ann Neurol 2007;61:120-129 (Pubitemid 46363839)
111. Hammack BN, Fung KY, Hunsucker SW, et al. Proteomic analysis of multiple sclerosis cerebrospinal fluid. Multiple Sclerosis 2004;10:245-260 (Pubitemid 38807450)
112. Teunissen CE, Lutjohann D, von Bergmann K, et al. Combination of serum markers related to several mechanisms in Alzheimer's disease. Neurobiol Aging 2003;24:893-902 (Pubitemid 36962973)
113. Hye A, Lynham S, Thambisetty M, et al. Proteome-based plasma biomarkers for Alzheimer's disease. Brain 2006;129:3042-3050 (Pubitemid 44684524)
114. Rosenmann H, Meiner Z, Geylis V, et al. Detection of circulating antibodies against tau protein in its unphosphorylated and in its neurofibrillary tangles-related phosphorylated state in Alzheimer's disease and healthy subjects. Neurosci Lett 2006;410:90-93 (Pubitemid 44709405)
115. Ray S, Britschgi M, Herbert S, et al. Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins. Nature Med 2007;13:1359-62 •• A large-scale study that demonstrates AD can be diagnosed by measurement of 18 cytokines in plasma.
116. Maes OC, Xu S, Yu B, et al. Transcriptional profiling of Alzheimer blood mononuclear cells by microarray. Neurobiol Aging 2007;28:1795-809 •• A study that demonstrates altered gene transcription in peripheral blood mononuclear cells from AD patients.
117. Kalman J, Kitajka K, Pakaski M, et al. Gene expression profile analysis of lymphocytes from Alzheimer's patients. Psychiatr Genet 2005;15:1-6 •• A study that demonstrates altered gene transcription in peripheral blood lymphocytes from AD patients.
118. Colangelo V, Schurr J, Ball MJ, et al. Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling. J Neurosci Res 2002;70:462-473 (Pubitemid 35222383)
119. Yao PJ, Zhu M, Pyun EI, et al. Defects in expression of genes related to synaptic vesicle trafficking in frontal cortex of Alzheimer's disease. Neurobiol Dis 2003;12:97-109 (Pubitemid 36355860)
120. Blalock EM, Geddes JW, Chen KC, et al. Incipient Alzheimer's disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc Natl Acad Sci USA 2004;101:2173-2178 (Pubitemid 38229034)
121. Ho L, Xiang Z, Mukherjee P, et al. Gene expression profiling of the tau mutant (P301L) transgenic mouse brain. Neurosci Lett 2001;310:1-4 (Pubitemid 32778470)
122. Dickey CA, Loring JF, Montgomery J, et al. Selectively reduced expression of synaptic plasticity-related genes in amyloid precursor protein + presenilin-1 transgenic mice. J Neurosci 2003;23:5219-5226 (Pubitemid 36793250)
123. Reddy PH, McWeeney S, Park BS, et al. Gene expression profiles of transcripts in amyloid precursor protein transgenic mice: up-regulation of mitochondrial metabolism and apoptotic genes is an early cellular change in Alzheimer's disease. Hum Mol Genet 2004;13:1225-1240 (Pubitemid 38877876)
124. Paccalin M, Pain-Barc S, Pluchon C, et al. Activated mTOR and PKR kinases in lymphocytes correlate with memory and cognitive decline in Alzheimer's disease. Dement Geriatr Cogn Disord 2006;22:320-326 (Pubitemid 44651446)
125. de las Cuevas N, Munoz U, Hermida OG, Martin-Requero A. Altered transcriptional regulators in response to serum in immortalized lymphocytes from Alzheimer's disease patients. Neurobiol Aging 2005;26:615-624
126. Hye A, Kerr F, Archer N, et al. Glycogen synthase kinase-3 is increased in white cells early in Alzheimer's disease. Neurosci Lett 2005;373:1-4 (Pubitemid 39536210)
127. Beausoleil SA, Jedrychowski M, Schwartz D, et al. Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci USA 2004;101:12130-12135 (Pubitemid 39145408)
128. Olsen JV, Blagoev B, Gnad F, et al. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2006;127:635-648 (Pubitemid 44647421)
129. Bodenmiller B, Malmstrom J, Gerrits B, et al. PhosphoPep-a phosphoproteome resource for systems biology research in Drosophila Kc167 cells. Mol Syst Biol 2007;3:139 (Pubitemid 47587027)
130. Kim SY, Chudapongse N, Lee SM, et al. Proteomic analysis of phosphotyrosyl proteins in the rat brain: effect of butorphanol dependence. J Neurosci Res 2004;77:867-877 (Pubitemid 39187069)
131. Yoo GH, Piechocki MP, Ensley JF, et al. Clinical Cancer Res 2002;8:3910-3921
132. Wenner BR, Lovell MA, Lynn BC. Proteomic analysis of human ventricular cerebrospinal fluid from neurologically normal, elderly subjects using two-dimensional LC-MS/MS. J Proteome Res 2004;3:97-103 (Pubitemid 38233456)
133. Yuan X, Desiderio DM. Proteomics analysis of prefractionated human lumbar cerebrospinal fluid. Proteomics 2005;5:541-550 (Pubitemid 40262071)
134. Fountoulakis M. Application of proteomics technologies in the investigation of the brain. Mass Spectrom Rev 2004;23:231-258
135. Arendt T. Synaptic plasticity and cell cycle activation in neurons are alternative effector pathways: the 'Dr. Jekyll and Mr. Hyde concept' of Alzheimer's disease or the yin and yang of neuroplasticity. Prog Neurobiol 2003;71:83-248 • It is proposed that AD may arise from the inappropriate entry of neurons into the cell cycle.
136. Hoerndli FJ, Pelech S, Papassotiropoulos A, Götz J. Abeta treatment and P301L tau expression in an Alzheimer's disease tissue culture model act synergistically to promote aberrant cell cycle re-entry. Eur J Neurosci 2007;26:60-72 (Pubitemid 47035431)
137. Pronin AN, Morris AJ, Surguchov A, Benovic JL. Synucleins are a novel class of substrates for G protein-coupled receptor kinases. J Biol Chem 2000;275:26515-26525 (Pubitemid 30676709)
138. Li X, Alafuzoff I, Soininen H, et al. Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer's disease brain. FEBS J 2005;272:4211-4220 (Pubitemid 41160927)
139. Milton NG. Phosphorylation of amyloid-beta at the serine 26 residue by human cdc2 kinase. Neuroreports 2001;12:3839-3844 (Pubitemid 33105182)
140. Pearson AG, Byrne UT, MacGibbon GA, et al. Activated c-Jun is present in neurofibrillary tangles in Alzheimer's disease brains. Neurosci Lett 2006;398:246-250 (Pubitemid 43673710)
141. Gu Y, Hamajima N, Ihara Y. Neurofibrillary tangle-associated collapsin response mediator protein-2 (CRMP-2) is highly phosphorylated on Thr-509, Ser-518, and Ser-522. Biochemistry 2000;39:4267-4275 (Pubitemid 30212642)
142. Johnson G, Gotlib J, Haroutunian V, et al. Increased phosphorylation of elongation factor 2 in Alzheimer's disease. Brain Res Mol Brain Res 1992;15:319-326
143. Atzori C, Ghetti B, Piva R, et al. Activation of the JNK/p38 pathway occurs in diseases characterized by tau protein pathology and is related to tau phosphorylation but not to apoptosis. J Neuropathol Exp Neurol 2001;60:1190-1197 (Pubitemid 33117099)
144. Ogawa O, Lee HG, Zhu X, et al. Increased p27, an essential component of cell cycle control, in Alzheimer's disease. Aging Cell 2003;2:105-110
145. Mei M, Su B, Harrison K, et al. Distribution, levels and phosphorylation of Raf-1 in Alzheimer's disease. J Neurochem 2006;99:1377-1388 (Pubitemid 44730092)
146. Hoesen G, Ksiezak-Reding H. Phosphorylation of tau by fyn: implications for Alzheimer's disease. J Neurosci 2004;24:2304-2312 (Pubitemid 38314562)
147. Augustinack JC, Schneider A, Mandelkow EM, Hyman BT. Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease. Acta Neuropathol (Berlin) 2002;103:26-33 (Pubitemid 36075309)
148. Maurage CA, Sergeant N, Ruchoux MM, et al. Phosphorylated serine 199 of microtubule-associated protein tau is a neuronal epitope abundantly expressed in youth and an early marker of tau pathology. Acta Neuropathol (Berl) 2003;105:89-97 (Pubitemid 36798793)
149. Ferrer I, Barrachina M, Puig B. Glycogen synthase kinase-3 is associated with neuronal and glial hyperphosphorylated tau deposits in Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration. Acta Neuropathol (Berlin) 2002;104:583-591 (Pubitemid 36075423)
150. Ferrer I, Barrachina M, Puig B. Anti-tau phospho-specific Ser262 antibody recognizes a variety of abnormal hyper-phosphorylated tau deposits in tauopathies including Pick bodies and argyrophilic grains. Acta Neuropathol (Berl) 2002;104:658-664 (Pubitemid 36075431)
151. Yoshimura Y, Ichinose T, Yamauchi T. Phosphorylation of tau protein to sites found in Alzheimer's disease brain is catalyzed by Ca2+/calmodulin- dependent protein kinase II as demonstrated tandem mass spectrometry. Neurosci Lett 2003;353:185-188 (Pubitemid 37510173)
152. Reynolds CH, Betts JC, Blackstock WP, et al. Phosphorylation sites on tau identified by nanoelectrospray mass spectrometry: differences in vitro between the mitogen-activated protein kinases ERK2, c-Jun N-terminal kinase and P38, and glycogen synthase kinase-3beta. J Neurochem 2000;74:1587-1595 (Pubitemid 30163980)
153. Hashiguchi M, Saito T, Hisanaga S, Hashiguchi T. Truncation of CDK5 activator p35 induces intensive phosphorylation of Ser202/Thr205 of human tau. J Biol Chem 2002;277:44525-44530 (Pubitemid 36157887)
154. Biernat J, Wu YZ, Timm T, et al. Protein kinase MARK/PAR-1 is required for neurite outgrowth and establishment of neuronal polarity. Mol Biol Cell 2002;13:4013-4402 (Pubitemid 35398567)
155. Maccioni RB, Otth C, Concha II, Munoz JP. The protein kinase Cdk5. Structural aspects, roles in neurogenesis and involvement in Alzheimer's pathology. Eur J Biochem 2001;268:1518-1527 (Pubitemid 32862683)
156. Jicha GA, Weaver C, Lane E, et al. cAMP-dependent protein kinase phosphorylations on tau in Alzheimer's disease. J Neurosci 1999;19:7486-7494 (Pubitemid 29404605)
157. Gotz J, Nitsch RM. Compartmentalized tau hyperphosphorylation and increased levels of kinases in transgenic mice. Neuroreport 2001;12:2007-2016 (Pubitemid 32553723)
158. Chohan MO, Khatoon S, Iqbal IG, Iqbal K. Involvement of I2PP2A in the abnormal hyperphosphorylation of tau and its reversal by Memantine. FEBS Lett 2006;580:3973-3979 (Pubitemid 43946883)
159. Evans DB, Rank KB, Bhattacharya K, et al. Tau phosphorylation at serine 396 and serine 404 by human recombinant tau protein kinase II inhibits tau's ability to promote microtubule assembly. J Biol Chem 2003;278:24977-24983 (Pubitemid 30626606)