1 Scheltens, P. et al. Alzheimer's disease. Lancet 388, 505-517, doi:10.1016/S0140-6736(15)01124-1 (2016).
2 Olsson, B. et al. CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Lancet Neurol 15, 673-684, doi:10.1016/S1474-4422(16)00070-3 (2016).
3 Hansson, O. et al. Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 5, 228-234, doi:10.1016/S1474-4422(06)70355-6 (2006).
4 Shaw, L. M. et al. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol 65, 403-413, doi:10.1002/ana.21610 (2009).
5 Vos, S. J. et al. Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study. Lancet Neurol 12, 957-965, doi:10.1016/S1474-4422(13)70194-7 (2013).
6 Schindler, S. E. et al. Emerging cerebrospinal fluid biomarkers in autosomal dominant Alzheimer's disease. Alzheimers Dement 15, 655-665, doi:10.1016/j.jalz.2018.12.019 (2019).
7 Jack, C. R., Jr. et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement 14, 535-562, doi:10.1016/j.jalz.2018.02.018 (2018).
8 Riemenschneider, M. et al. Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt-Jakob disease from other dementias. Mol Psychiatry 8, 343-347, doi:10.1038/sj.mp.4001220 (2003).
9 Skillback, T. et al. Diagnostic performance of cerebrospinal fluid total tau and phosphorylated tau in Creutzfeldt-Jakob disease: results from the Swedish Mortality Registry. JAMA Neurol 71, 476-483, doi:10.1001/jamaneurol.2013.6455 (2014).
10 Schoonenboom, N. S. et al. Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort. Neurology 78, 47-54, doi:10.1212/WNL.0b013e31823ed0f0 (2012).
11 Hampel, H. et al. Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheimer disease: a comparative cerebrospinal fluid study. Arch Gen Psychiatry 61, 95-102, doi:10.1001/archpsyc.61.1.95 (2004).
12 Leuzy, A. et al. Diagnostic Performance of RO948 F 18 Tau Positron Emission Tomography in the Differentiation of Alzheimer Disease From Other Neurodegenerative Disorders. JAMA Neurol, doi:10.1001/jamaneurol.2020.0989 (2020).
13 La Joie, R. et al. Associations between [(18)F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample. Neurology 90, e282-e290, doi:10.1212/WNL.0000000000004860 (2018).
14 Maia, L. F. et al. Changes in amyloid-beta and Tau in the cerebrospinal fluid of transgenic mice overexpressing amyloid precursor protein. Sci Transl Med 5, 194re192, doi:10.1126/scitranslmed.3006446 (2013).
15 Schelle, J. et al. Prevention of tau increase in cerebrospinal fluid of APP transgenic mice suggests downstream effect of BACE1 inhibition. Alzheimers Dement 13, 701-709, doi:10.1016/j.jalz.2016.09.005 (2017).
16 De Felice, F. G. et al. Alzheimer's disease-type neuronal tau hyperphosphorylation induced by A beta oligomers. Neurobiol Aging 29, 1334-1347, doi:10.1016/j.neurobiolaging.2007.02.029 (2008).
17 Sackmann, C. & Hallbeck, M. Oligomeric amyloid-beta induces early and widespread changes to the proteome in human iPSC-derived neurons. Sci Rep 10, 6538, doi:10.1038/s41598-020-63398-6 (2020).
18 Barthelemy, N. R. et al. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer's disease. Nat Med 26, 398-407, doi:10.1038/s41591-020-0781-z (2020).
19 Sato, C. et al. Tau Kinetics in Neurons and the Human Central Nervous System. Neuron 97, 1284-1298 e1287, doi:10.1016/j.neuron.2018.02.015 (2018).
20 Bateman, R. J. et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med 367, 795-804, doi:10.1056/NEJMoa1202753 (2012).
21 Toledo, J. B., Xie, S. X., Trojanowski, J. Q. & Shaw, L. M. Longitudinal change in CSF Tau and Abeta biomarkers for up to 48 months in ADNI. Acta Neuropathol 126, 659-670, doi:10.1007/s00401-013-1151-4 (2013).
22 Brunello, C. A., Merezhko, M., Uronen, R. L. & Huttunen, H. J. Mechanisms of secretion and spreading of pathological tau protein. Cell Mol Life Sci 77, 1721-1744, doi:10.1007/s00018-019-03349-1 (2020).
23 Ishiguro, K. et al. Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease. Neurosci Lett 270, 91-94, doi:10.1016/s0304-3940(99)00476-0 (1999).
24 Janelidze, S. et al. Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer's disease. Nat Commun 11, 1683, doi:10.1038/s41467-020-15436-0 (2020).
25 Russell, C. L. et al. Comprehensive Quantitative Profiling of Tau and Phosphorylated Tau Peptides in Cerebrospinal Fluid by Mass Spectrometry Provides New Biomarker Candidates. J Alzheimers Dis 55, 303-313, doi:10.3233/JAD-160633 (2017).
26 Buerger, K. et al. Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231. Arch Neurol 59, 1267-1272, doi:10.1001/archneur.59.8.1267 (2002).
27 Barthelemy, N. R. et al. Cerebrospinal fluid phospho-tau T217 outperforms T181 as a biomarker for the differential diagnosis of Alzheimer's disease and PET amyloid-positive patient identification. Alzheimers Res Ther 12, 26, doi:10.1186/s13195-020-00596-4 (2020).
28 Karikari, T. K. et al. Head-to-head comparison of clinical performance of CSF phospho-tau T181 and T217 biomarkers for Alzheimer's disease diagnosis. Alzheimers Dement, doi:10.1002/alz.12236 (2020).
29 Suarez-Calvet, M. et al. Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer's continuum when only subtle changes in Abeta pathology are detected. EMBO Mol Med, e12921, doi:10.15252/emmm.202012921 (2020).
30 Uhlmann, R. E. et al. Acute targeting of pre-amyloid seeds in transgenic mice reduces Alzheimer-like pathology later in life. Nat Neurosci 23, 1580-1588, doi:10.1038/s41593-020-00737-w (2020).
31 Horowitz, P. M. et al. Early N-terminal changes and caspase-6 cleavage of tau in Alzheimer's disease. J Neurosci 24, 7895-7902, doi:10.1523/JNEUROSCI.1988-04.2004 (2004).
32 De Vos, A. A novel conformational, phospho-Threonine 231 specific assay for CSF protein tau. J Prev Alzheimers Dis (2016).
33 Cselenyi, Z. et al. Clinical validation of 18F-AZD4694, an amyloid-beta-specific PET radioligand. J Nucl Med 53, 415-424, doi:10.2967/jnumed.111.094029 (2012).
34 Pascoal, T. A. et al. In vivo quantification of neurofibrillary tangles with [(18)F]MK-6240. Alzheimers Res Ther 10, 74, doi:10.1186/s13195-018-0402-y (2018).
35 Therriault, J. et al. Association of Apolipoprotein E epsilon4 With Medial Temporal Tau Independent of Amyloid-beta. JAMA Neurol 77, 470-479, doi:10.1001/jamaneurol.2019.4421 (2020).
36 Pascoal, T. A. et al. 18F-MK-6240 PET for early and late detection of neurofibrillary tangles. Brain 143, 2818-2830, doi:10.1093/brain/awaa180 (2020).
37 Pascoal, T. A. et al. Amyloid and tau signatures of brain metabolic decline in preclinical Alzheimer's disease. Eur J Nucl Med Mol Imaging 45, 1021-1030, doi:10.1007/s00259-018-3933-3 (2018).
38 Therriault, J. et al. Determining Amyloid-beta positivity using [(18)F]AZD4694 PET imaging. J Nucl Med, doi:10.2967/jnumed.120.245209 (2020).
39 Klunk, W. E. et al. The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement 11, 1-15 e11-14, doi:10.1016/j.jalz.2014.07.003 (2015).
40 Rowe, C. C. et al. Standardized Expression of 18F-NAV4694 and 11C-PiB beta-Amyloid PET Results with the Centiloid Scale. J Nucl Med 57, 1233-1237, doi:10.2967/jnumed.115.171595 (2016).
41 Braak, H. & Braak, E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82, 239-259, doi:10.1007/BF00308809 (1991).
42 Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H. & Del Tredici, K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol 112, 389-404, doi:10.1007/s00401-006-0127-z (2006).
43 Mathotaarachchi, S. et al. VoxelStats: A MATLAB Package for Multi-Modal Voxel-Wise Brain Image Analysis. Front Neuroinform 10, 20, doi:10.3389/fninf.2016.00020 (2016).
44 Worsley, K. J., Taylor, J. E., Tomaiuolo, F. & Lerch, J. Unified univariate and multivariate random field theory. Neuroimage 23 Suppl 1, S189-195, doi:10.1016/j.neuroimage.2004.07.026 (2004).
45 Wu, J. W. et al. Small misfolded Tau species are internalized via bulk endocytosis and anterogradely and retrogradely transported in neurons. J Biol Chem 288, 1856-1870, doi:10.1074/jbc.M112.394528 (2013).
46 Mirbaha, H., Holmes, B. B., Sanders, D. W., Bieschke, J. & Diamond, M. I. Tau Trimers Are the Minimal Propagation Unit Spontaneously Internalized to Seed Intracellular Aggregation. J Biol Chem 290, 14893-14903, doi:10.1074/jbc.M115.652693 (2015).
47 Santos, J. R. F. et al. Validation of a prototype tau Thr231 phosphorylation CSF ELISA as a potential biomarker for Alzheimer's disease. J Neural Transm (Vienna) 126, 339-348, doi:10.1007/s00702-019-01982-5 (2019).
48 Spiegel, J. et al. Greater specificity for cerebrospinal fluid P-tau231 over P-tau181 in the differentiation of healthy controls from Alzheimer's disease. J Alzheimers Dis 49, 93-100, doi:10.3233/JAD-150167 (2016).
49 Blennow, K., Vanmechelen, E. & Hampel, H. CSF total tau, Abeta42 and phosphorylated tau protein as biomarkers for Alzheimer's disease. Mol Neurobiol 24, 87-97, doi:10.1385/MN:24:1-3:087 (2001).
50 Glodzik-Sobanska, L. et al. The effects of normal aging and ApoE genotype on the levels of CSF biomarkers for Alzheimer's disease. Neurobiol Aging 30, 672-681, doi:10.1016/j.neurobiolaging.2007.08.019 (2009).
51 Kidemet-Piskac, S. et al. Evaluation of cerebrospinal fluid phosphorylated tau231 as a biomarker in the differential diagnosis of Alzheimer's disease and vascular dementia. CNS Neurosci Ther 24, 734-740, doi:10.1111/cns.12814 (2018).
52 Mitchell, A. J. CSF phosphorylated tau in the diagnosis and prognosis of mild cognitive impairment and Alzheimer's disease: a meta-analysis of 51 studies. J Neurol Neurosurg Psychiatry 80, 966-975, doi:10.1136/jnnp.2008.167791 (2009).
53 Augustinack, J. C., Schneider, A., Mandelkow, E. M. & Hyman, B. T. Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease. Acta Neuropathol 103, 26-35, doi:10.1007/s004010100423 (2002).
54 Ercan-Herbst, E. et al. A post-translational modification signature defines changes in soluble tau correlating with oligomerization in early stage Alzheimer's disease brain. Acta Neuropathol Commun 7, 192, doi:10.1186/s40478-019-0823-2 (2019).
55 Castellani, R. J. & Perry, G. Tau Biology, Tauopathy, Traumatic Brain Injury, and Diagnostic Challenges. J Alzheimers Dis 67, 447-467, doi:10.3233/JAD-180721 (2019).
56 Amniai, L. et al. Alzheimer disease specific phosphoepitopes of Tau interfere with assembly of tubulin but not binding to microtubules. FASEB J 23, 1146-1152, doi:10.1096/fj.08-121590 (2009).
57 Palmqvist, S. et al. Earliest accumulation of beta-amyloid occurs within the default-mode network and concurrently affects brain connectivity. Nat Commun 8, 1214, doi:10.1038/s41467-017-01150-x (2017).
58 Malarte, M. L., Nordberg, A. & Lemoine, L. Characterization of MK6240, a tau PET tracer, in autopsy brain tissue from Alzheimer's disease cases. Eur J Nucl Med Mol Imaging, doi:10.1007/s00259-020-05035-y (2020).
59 Blennow, K. & Hampel, H. CSF markers for incipient Alzheimer's disease. Lancet Neurol 2, 605-613, doi:10.1016/s1474-4422(03)00530-1 (2003).
60 Mattsson-Carlgren, N. et al. Abeta deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer's disease. Sci Adv 6, eaaz2387, doi:10.1126/sciadv.aaz2387 (2020).
61 Gordon, B. A. et al. Tau PET in autosomal dominant Alzheimer's disease: relationship with cognition, dementia and other biomarkers. Brain 142, 1063-1076, doi:10.1093/brain/awz019 (2019).
62 Pooler, A. M., Phillips, E. C., Lau, D. H., Noble, W. & Hanger, D. P. Physiological release of endogenous tau is stimulated by neuronal activity. EMBO Rep 14, 389-394, doi:10.1038/embor.2013.15 (2013).
63 Sutphen, C. L. et al. Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal injury in symptomatic late onset Alzheimer's disease. Alzheimers Dement 14, 869-879, doi:10.1016/j.jalz.2018.01.012 (2018).