Intraneuronal tau aggregation precedes diffuse plaque deposition, but amyloid-β changes occur before increases of tau in cerebrospinal fluid

Acta Neuropathologica

Volumn 126, Issue 5, 2013, Pages 631-641

  Braak, Heiko ^a   Zetterberg, Henrik ^b,c   Del Tredici, Kelly ^a   Blennow, Kaj ^b  

^a UNIVERSITY OF ULM   (Germany)

^b SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Abnormal tau protein; Alzheimer's disease; Amyloid protein; Cerebrospinal fluid; Diffuse plaques; Neurofibrillary tangles; Pretangles; Tau

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; BIOLOGICAL MARKER; TAU PROTEIN;

ALZHEIMER DISEASE; AUTOPHAGY; CELL SURVIVAL; DISEASE COURSE; HUMAN; MINI MENTAL STATE EXAMINATION; NERVE CELL NECROSIS; NEUROFIBRILLARY TANGLE; NEUROPATHOLOGY; NEUROPIL THREAD; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN ANALYSIS; PROTEIN CEREBROSPINAL FLUID LEVEL; PROTEIN CLEAVAGE; PROTEIN CONFORMATION; PROTEIN PHOSPHORYLATION; REVIEW; SYMPTOM;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; DISEASE PROGRESSION; HUMANS; NEUROFIBRILLARY TANGLES; NEURONS; TAU PROTEINS;

EID: 84888205849     PISSN: 00016322     EISSN: 14320533     Source Type: Journal    
DOI: 10.1007/s00401-013-1139-0     Document Type: Review

References (130)

1. Albert MS, Dekosky ST, Dickson D et al (2011) The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7:270-279
2. Alonso AC, Li B, Grundke-Iqbal I et al (2008) Mechanism of tau-induced neurodegeneration in Alzheimer disease and related tauopathies. Curr Alzheimer Res 5:375-384
3. Amieva H, le Goff M, Millet X et al (2008) Prodromal Alzheimer's disease: successive emergence of clinical symptoms. Ann Neurol 64:492-498
4. Andreasen N, Hesse C, Davidsson P et al (1999) Cerebrospinal fluid β-amyloid(1-42) in Alzheimer's disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. Arch Neurol 56:673-680
5. Andreasen N, Minthon L, Vanmechelen E et al (1999) Cerebrospinal fluid tau and Abeta42 as predictors of development of Alzheimer's disease in patients with mild cognitive impairment. Neurosci Lett 273:5-8
6. Arai H, Terajima M, Miura M et al (1995) Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer's disease. Ann Neurol 38:649-652
7. Arnold SE, Hyman BT, Flory J et al (1991) The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. Cerebr Cortex 1:103-116
8. Baas PW (2002) Microtubule transport in the axon. Int Rev Cytol 212:41-62
9. Ballatore C, Lee VMY, Trojanowski JQ (2007) Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nature Rev Neurosci 8:663-672
10. Bancher C, Brunner C, Lassmann H et al (1989) Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease. Brain Res 477:90-99
11. Bateman RJ, Xiong C, Benzinger TL, Dominantly Inherited Alzheimer Network et al (2012) Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med 367:795-804
12. Blennow K (2004) Cerebrospinal fluid protein biomarkers for Alzheimer's disease. NeuroRx 1:213-225
13. Blennow K, Hampel H (2003) Cerebrospinal fluid markers for incipient Alzheimer's disease. Lancet Neurol 2:605-613
14. Blennow K, Wallin A, Agren H et al (1995) Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease? Mol Chem Neuropathol 26:231-245
15. Blennow K, Zetterberg H, Minthon L et al (2007) Longitudinal stability of CSF biomarkers in Alzheimer's disease. Neurosci Lett 419:18-22
16. Blennow K, Hampel H, Weiner M, Zetterberg H (2010) Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 6:131-144
17. Blennow K, Hardy J, Zetterberg H (2012) The neuropathology and neurobiology of traumatic brain injury. Neuron 76:886-899
18. Blennow K, Zetterberg H, Fagan AM (2012) Fluid biomarkers in Alzheimer's disease. Cold Spring Harb Perspect Med 2:a006221
19. Blom ES, Giedraitis V, Zetterberg H et al (2009) Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype. Dement Geriatr Cogn Disord 27:458-464
20. Bobinski M, Wegiel J, Tarnawski M et al (1998) Duration of neurofibrillary changes in the hippocampal pyramidal neurons. Brain Res 799:156-158
21. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239-259
22. Braak H, del Tredici K (2004) Alzheimer's disease: intraneuronal alterations precede insoluble amyloid-β formation. Neurobiol Aging 25:713-718
23. Braak H, del Tredici K (2011) The pathological process underlying Alzheimer's disease in individuals under thirty. Acta Neuropathol 121:171-181
24. Braak H, del Tredici K (2012) Alzheimer's disease: pathogenesis and prevention. Alzheimers Dement 8:227-233
25. Braak H, del Tredici K (2012) Where, when, and in what form does sporadic Alzheimer's disease begin? Curr Opin Neurol 25:708-714
26. Braak H, del Tredici K (2013) Evolutional aspects of Alzheimer's disease pathogenesis. J Alzheimer Dis 30(Suppl 1):155-161
27. Braak H, Thal DR, Ghebremedhin E et al (2011) Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol 70:960-969
28. Buchhave P, Minthon L, Zetterberg H et al (2012) Cerebrospinal fluid levels of β-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia. Arch Gen Psychiatry 69:98-106
29. Buerger K, Ewers M, Pirttilä T et al (2006) CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease. Brain 129:3035-3041
30. Cowan CM, Bossing T, Page A et al (2010) Soluble hyper-phosphorylated tau causes microtubule breakdown and functionally compromises normal tau in vivo. Acta Neuropathol 120:593-604
31. Degerman Gunnarsson M, Lindau M, Wall A et al (2010) Pittsburgh Compound-B and Alzheimer's disease biomarkers in CSF, plasma and urine: an exploratory study. Dement Geriatr Cogn Disord 29:204-212
32. Dolan D, Troncoso J, Resnick SM et al (2010) Age, Alzheimer's disease and dementia in the Baltimore Longitudinal Study of Ageing. Brain 133:2225-2231
33. Dong S, Duan Y, Hu Y, Zhao Z (2012) Advances in the pathogenesis of Alzheimer's disease: a re-evaluation of amyloid cascade hypothesis. Transl Neurodegener 1:1-12
34. Duyckaerts C, Delatour B, Potier MC (2009) Classification and basic pathology of Alzheimer's disease. Acta Neuropathol 118:5-36
35. Elobeid A, Soininen H, Alafuzoff I (2011) Hyperphosphorylated tau in young and middle-aged subjects. Acta Neuropathol 123:97-104
36. Fagan AM, Mintun MA, Mach RH et al (2006) Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol 59:512-519
37. Fagan AM, Roe CM, Xiong C et al (2007) Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol 64:343-349
38. Fewster PH, Griffin-Brooks S, MacGregor J et al (1991) A topographical pathway by which histopathological lesions disseminate through the brain of patients with Alzheimer's disease. Dement Geriatr Cogn Disord 2:121-132
39. Fillenbaum GG, van Belle G, Morris JC et al (2008) CERAD (Consortium to establish a registry for Alzheimer's disease) The first 20 years. Alzheimers Dement 4:96-109
40. Fodero-Tavoletti MT, Okamura N, Furumoto S et al (2011) 18F-THK523: a novel in vivo tau imaging ligand for Alzheimer's disease. Brain 134:1089-1100
41. Galvan V, Gorostiza OF, Banweit S et al (2006) Reversal of Alzheimer's-like pathology and behavior in human APP transgenic mice by mutation of Asp664. Proc Natl Acad Sci USA 103:7130-7135
42. Giannakopoulos P, Herrmann FR, Bussiere T et al (2003) Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 60:1495-1500
43. Goedert M, Klug A, Crowther RA (2006) Tau protein, the paired helical filament and Alzheimer's disease. J Alzheimers Dis 9(Suppl):195-207
44. Grimmer T, Henriksen G, Wester HJ et al (2009) Clinical severity of Alzheimer's disease is associated with PiB uptake in PET. Neurobiol Aging 30:1902-1909
45. Grimmer T, Riemenschneider M, Förstl H et al (2009) Beta amyloid in Alzheimer's disease: increased deposition in brain is reflected in reduced concentration in cerebrospinal fluid. Biol Psychiatry 65:927-934
46. Guillozet AL, Weintraub S, Mash DC et al (2003) Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment. Arch Neurol 60:729-736
47. Gustafson DR, Skoog I, Rosengren L et al (2007) Cerebrospinal fluid β-amyloid 1-42 concentration may predict cognitive decline in older women. J Neurol Neurosurg Psychiatry 78:461-464
48. Hall GF (2012) The biology and pathobiology of tau protein. In: Kavallaris M (ed) The cytoskeleton and human disease. Springer, New York, pp 285-313
49. Hall GF, Saman S (2012) Death or secretion? The demise of a plausible assumption about CSF-tau in Alzheimer disease? Commun Integrat Biol 5:1-4
50. Hardy JA (2006) Alzheimer's disease: the amyloid cascade hypothesis: an update and reappraisal. J Alzheimers Dis 9:151-153
51. Hardy JA, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297:353-356
52. Hesse C, Rosengren L, Vanmechelen E et al (2000) Cerebrospinal fluid markers for Alzheimer's disease evaluated after acute ischemic stroke. J Alzheimer Dis 2:199-206
53. Hesse C, Rosengren L, Andreasen N et al (2001) Transient increase in CSF total tau but not phospho-tau after acute stroke. Neurosci Lett 297:187-190
54. Hyman BT, Goméz-Isla T (1994) Alzheimer's disease is a laminar, regional, and neural system specific disease, not a global brain disease. Neurobiol Aging 15:353-354
55. Hyman BT, Phelps CH, Beach TG et al (2012) National institute on aging-Alzheimer's association guidelines for the neuropathologic assessment of Alzheimer's disease. Alheimers Dement 8:1-13
56. Ikonomovic MD, Klunk WE, Abrahamson EE et al (2008) Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain 131:1630-1645
57. Iqbal K, Grundke-Iqbal I (2008) Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention. J Cell Mol Med 12:38-55
58. Iqbal K, Liu F, Gong CX et al (2009) Mechanisms of tau-induced neurodegeneration. Acta Neuropathol 118:53-69
59. Jack CR Jr, Knopman DS, Jagust WJ et al (2010) Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol 9:119-128
60. Jack CR Jr, Knopman DS, Jagust WJ et al (2013) Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 12:207-216
61. Jeganathan S, von Bergen M, Mandelkow EM et al (2008) The natively unfolded character of tau and its aggregation to Alzheimer-like paired helical filaments. Biochemistry 47:10526-10539
62. Jensen JR, Cisek K, Funk KE et al (2011) Research towards tau imaging. J Alzheimers Dis 26(Suppl 3):147-157
63. Karran E, Mercken M, de Strooper B (2011) The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov 10:698-712
64. Klunk WE, Engler H, Nordberg A et al (2004) Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol 55:306-319
65. Korczyn AD (2008) The amyloid cascade hypothesis. Alzheimers Dement 4:176-178
66. Kovacech B, Skrabana R, Novak M (2010) Transition of tau protein from disordered to misordered in Alzheimer's disease. Neurodegener Dis 7:24-27
67. Le S, Kim W, Li Z, McKee AC, Hall GF (2012) Accumulation of vesicle-associated human tau in distal dendrites drives degeneration and tau secretion in an in situ cellular tauopathy model. Int J Alzheimers Dis 2012:172837. doi: 10.1155/2012/172837
68. Lee HG, Casadesus G, Zhu X et al (2004) Perspectives on the amyloid-beta cascade hypothesis. J Alzheimers Dis 6:137-145
69. Lee HG, Zhu K, Castellani RJ et al (2007) Amyloid-beta in Alzheimer disease: the null versus the alternate hypotheses. J Pharmacol Exp Ther 321:823-829
70. Li B, Chohan MO, Grundke-Iqbal I et al (2007) Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau. Acta Neuropathol 113:501-511
71. Liu F, Xue ZQ, Deng SH, et al (2013) γ-Secretase binding sites in aged and Alzheimer's disease human cerebrum: the choroid plexus as a putative origin of CSF Aβ. Eur J Neurosci 12159 [Epub ahead of print]. doi: 10.1111/ejn
72. Mandelkow EM, Mandelkow E (2012) Biochemistry and cell biology of tau protein in neurofibrillary degeneration. Cold Spring Harb Perspect Med 2:a006247
73. Mandelkow E, von Bergen M, Biernat J et al (2007) Structural principles of tau and the paired helical filaments of Alzheimer's disease. Brain Pathol 17:83-90
74. Markesbery WR, Schmitt FA, Kryscio RJ et al (2006) Neuropathologic substrate of mild cognitive impairment. Arch Neurol 63:38-46
75. Masters CL, Selkoe DJ (2012) Biochemistry of amyloid β-protein and amyloid deposits in Alzheimer disease. Cold Spring Harb Perspect Med 2:a006262
76. Mattson MP (2004) Pathways towards and away from Alzheimer's disease. Nature 430:631-639
77. Mattsson N, Zetterberg H, Hansson O et al (2009) CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 302:385-393
78. Mattsson N, Portelius E, Rolstad S et al (2012) Longitudinal cerebrospinal fluid biomarkers over four years in mild cognitive impairment. J Alzheimers Dis 30:767-778
79. McKee A, Stein TD, Nowinski CJ et al (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136:43-64
80. Mirra S, Heyman A, McKeel D et al (1991) The consortium to establish a registry for Alzheimer's disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 41:479-486
81. Montine TJ, Phelps CH, Beach TG et al (2012) National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol 123:1-11
82. Moonis M, Swearer JM, Dayaw MP et al (2005) Familial Alzheimer disease: decreases in CSF Abeta42 levels precede cognitive decline. Neurology 65:323-325
83. Morsch R, Simon W, Coleman PD (1999) Neurons may live for decades with neurofibrillary tangles. J Neuropathol Exp Neurol 58:188-197
84. Motter R, Vigo-Pelfrey C, Kholodenko D et al (1995) Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease. Ann Neurol 38:643-648
85. Nelson PT, Jicha GA, Schmitt FA et al (2007) Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: neuritic plaques and neurofibrillary tangles "do count" when staging disease severity. J Neuropathol Exp Neurol 66:1136-1146
86. Nelson PT, Braak H, Markesbery WR (2009) Neuropathology and cognitive impairment in Alzheimer's disease: a complex but coherent relationship. J Neuropathol Exp Neurol 68:1-14
87. Nelson PT, Head E, Schmitt FA et al (2011) Alzheimer's disease is not "brain aging": neuropathological, genetic, and epidemiological human studies. Acta Neuropathol 121:571-587
88. Nelson PT, Alafuzoff I, Bigio EH et al (2012) Correlation of Alzheimer's disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol 71:362-381
89. Neselius S, Brisby H, Theodorsson A et al (2012) CSF-biomarkers in Olympic boxing: diagnosis and effects of repetitive head trauma. PLoS ONE 7(4):e33606
90. Olsson A, Vanderstichele H, Andreasen N et al (2005) Simultaneous measurement of β-amyloid(1-42), tau and phosphorylated tau (Thr181) in cerebrospinal fluid by the xMAP technology. Clin Chem 51:336-345
91. Öst M, Nylén K, Csajbok L, Olsson Öhrfelt A et al (2006) Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injury. Neurology 67:1600-1604
92. Otto M, Wiltfang J, Tumani H et al (1997) Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. Neurosci Lett 225:210-212
93. Pimplikar SW (2009) Reassessing the amyloid cascade hypothesis of Alzheimer's disease. Int J Biochem Cell Biol 41:1261-1268
94. Pooler AM, Phillips EC, Lau DHW et al (2013) Physiological release of endogenous tau is stimulated by neuronal activity. EMBO Rep 14:389-394
95. Rajendran L, Annaert W (2012) Membrane trafficking pathways in Alzheimer's disease. Traffic 13:759-770
96. Ringman JM, Younkin SG, Pratico D et al (2008) Biochemical markers in persons with preclinical familial Alzheimer disease. Neurology 71:85-92
97. Ringman JM, Coppola G, Elashoff D et al (2012) Cerebrospinal fluid biomarkers and proximity to diagnosis in preclinical familial Alzheimer's disease. Dement Geriatr Cogn Disord 33:1-5
98. Sabbagh MN, Cooper K, DeLange J et al (2010) Functional, global and cognitive decline correlates to accumulation of Alzheimer's pathology in MCI and AD. Curr Alzheimer Res 7:280-286
99. Saman S, Kim W, Raya M et al (2012) Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. J Biol Chem 287:3842-3849
100. Sämgård K, Zetterberg H, Blennow K et al (2010) Cerebrospinal fluid total tau as a marker of Alzheimer's disease intensity. Int J Geriatr Psychiatry 25:403-410
101. Schönheit B, Zarski R, Ohm TG (2004) Spatial and temporal relationships between plaques and tangles in Alzheimer-pathology. Neurobiol Aging 25:697-711
102. Selkoe DJ (1994) Alzheimer's disease: a central role for amyloid. J Neuropathol Exp Neurol 53:438-447
103. Selkoe DJ (2004) Aging, amyloid, and Alzheimer's disease: a perspective in honor of Carl Cotman. Neurochem Res 28:1703-1713
104. Selkoe DJ, Mandelkow E, Holtzman D (2012) Deciphering Alzheimer disease. Cold Spring Harb Perspect Med 2:1-8
105. Seubert P, Vigo-Pelfrey C, Esch F et al (1992) Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. Nature 359:325-327
106. Shaw LM, Vanderstichele H, Knapik-Czajka M, Alzheimer's Disease Neuroimaging Initiative et al (2009) Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol 65:403-413
107. Siemers ER (2009) How can we recognize "disease modification" effects? J Nutr Health Aging 13:341-343
108. Skoog I, Davidsson P, Aevarsson O et al (2003) Cerebrospinal fluid beta-amyloid 42 is reduced before the onset of sporadic dementia: a population-based study in 85-year-olds. Dement Geriatr Cogn Disord 15:169-176
109. Sperling RA, Eisen PS, Beckett LA et al (2011) Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7:280-292
110. Stomrud E, Hansson O, Blennow K et al (2007) Cerebrospinal fluid biomarkers predict decline in subjective cognitive function over 3 years in healthy controls. Dement Geriatr Cogn Disord 24:118-124
111. Strozyk D, Blennow K, White LR, Launer LJ (2003) CSF Aβ 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology 60:652-656
112. Sunderland T, Linker G, Mirza N et al (2003) Decreased beta-amyloid 1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer's disease. JAMA 289:2094-2103
113. Tapiola T, Alafuzoff I, Herukka SK et al (2009) Cerebrospinal fluid (beta)-amyloid 42 and tau proteins as biomarker changes in the brain. Arch Neurol 66:382-389
114. Tato RE, Frank A, Hernanz A (1995) Tau protein concentrations in cerebrospinal fluid of patients with dementia of the Alzheimer type. J Neurol Neurosurg Psychiatry 59:280-283
115. Thal DR, Rüb U, Schultz C et al (2000) Sequence of Aβ-protein deposition in the human medial temporal lobe. J Neuropathol Exp Neurol 59:733-748
116. Thal DR, Rüb U, Orantes M et al (2002) Phases of Aβ-deposition in the human brain and its relevance for the development of AD. Neurology 58:1791-1800
117. Uchihara T (2007) Silver diagnosis in neuropathology: principles, practice and revised interpretation. Acta Neuropathol 113:483-499
118. Uchihara T, Nakamura A, Yamazaki M, Mori O (2001) Evolution from pretangle neurons to neurofibrillary tangles monitored by thiazin red combined with Gallyas method and double immunofluorescence. Acta Neuropathol 101:535-539
119. Vanderstichele HM, Shaw L, Vandijck M, et al (2013) Alzheimer disease biomarker testing in cerebrospinal fluid: a method to harmonize assay platforms in the absence of an absolute reference standard. Clin Chem 25 January [ahead of print]. doi: 10.1373/clinchem.2012.201830
120. Vandermeeren M, Mercken M, Vanmechelen E et al (1993) Detection of tau proteins in normal and Alzheimer's disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay. J Neurochem 61:1828-1834
121. Vanmechelen E, Vanderstichele H, Davidsson P et al (2000) Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization. Neurosci Lett 285:49-52
122. van Rossum IA, Vos SJB, Burns L et al (2012) Injury markers predict cognitive decline in subjects with MCI and amyloid pathology. Neurology 79:1809-1816
123. Visser PJ, Verhey F, Knol DL et al (2009) Prevalence and prognostic value of cerebrospinal fluid markers of Alzheimer pathology in subjects with subjective cognitive impairment and mild cognitive impairment. The DESCRIPA study. Lancet Neurol 8:619-627
124. Vlassenko AG, Benzinger TL, Morris JC (2012) PET amyloid-beta imaging in preclinical Alzheimer's disease. Biochim Biophys Acta 1822:370-379
125. von Bergen M, Barghorn S, Biernat J et al (2005) Tau aggregation is driven by a transition from random coil to beta sheet structure. Biochim Biophys Acta 1739:158-166
126. Wallin ÅK, Blennow K, Andreasen N, Minthon L (2006) CSF biomarkers for Alzheimer's disease: levels of β-amyloid, tau and phosphorylated tau relate to clinical symptoms and survival. Dement Geriatr Cogn Disord 21:131-138
127. Weaver CL, Espinoza M, Kress Y et al (2000) Conformational change as one of the earliest alterations of tau in Alzheimer's disease. Neurobiol Aging 21:719-727
128. Zetterberg H, Hietala MA, Jonsson M et al (2006) Neurochemical aftermath of amateur boxing. Arch Neurol 63:1277-1280
129. Zetterberg H, Pedersen M, Lind K et al (2007) Intra-individual stability of CSF biomarkers for Alzheimer's disease over two years. J Alzheimers Dis 12:255-260
130. Zetterberg H, Tullhög K, Hansson O et al (2010) Low incidence of post-lumbar puncture headache in 1,089 consecutive memory clinic patients. Eur Neurol 63:326-330