Yanamandra K, Patel TK, Jiang H, Schindler S, Ulrich JD, Boxer AL, Miller BL, Kerwin DR, Gallardo G, Stewart F, Finn MB, Cairns NJ, Verghese PB, Fogelman I, West T, Braunstein J, Robinson G, Keyser J, Roh J, Knapik SS, Hu Y, Holtzman DM. (2017). Anti-tau antibody markedly increases plasma tau in mouse and man: Correlation with soluble brain tau. Science Translational Medicine. April 19, 2017.  Available at: http://dx.doi.org/10.1126/scitranslmed.aal2029

Ghosal K, Haag M, Verghese PB, West T, Veenstra T, Braunstein JB, Bateman RJ, Holtzman DM, Landreth GE (2016). A randomized controlled study to evaluate the effect of bexarotene on amyloid-β and apolipoprotein E metabolism in healthy subjects.  Alzheimer’s and Dementia 2:2. Available at: http://dx.doi.org/10.1016/j.trci.2016.06.001
  • SILKTM assay was used in a randomized placebo controlled study to assess the effect of the RXR agonist bexarotene on metabolism of amyloid beta isoforms as well as apoE in the human central nervous system. This study found that in spite of the low brain penetrance of the drug, bexarotene increased apoE concentrations in CSF by about 25% but had no effect on amyloid beta concentrations or metabolism.

Kester, M. I., Teunissen, C. E., Crimmins, D. L., Herries, E. M., Ladenson, J. H., Scheltens, P., … Fagan, A. M. (2015). Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease. JAMA Neurology, 1–7. Available at: http://doi.org/10.1001/jamaneurol.2015.1867

Kester, M. I., Teunissen, C. E., Sutphen, C., Herries, E. M., Ladenson, J. H., Xiong, C., … Fagan, A. M. (2015). Cerebrospinal fluid VILIP-1 and YKL-40, candidate biomarkers to diagnose, predict and monitor Alzheimer’s disease in a memory clinic cohort. Alzheimer’s Research & Therapy, 7(1), 59. Available at: http://doi.org/10.1186/s13195-015-0142-1

Sutphen, C. L., Jasielec, M. S., Shah, A. R., Macy, E. M., Xiong, C., Vlassenko, A. G., … Fagan, A. M. (2015). Longitudinal Cerebrospinal Fluid Biomarker Changes in Preclinical Alzheimer Disease During Middle Age. JAMA Neurology, 72(9), 1029–42. Available at: http://doi.org/10.1001/jamaneurol.2015.1285

Tarawneh, R., Head, D., Allison, S., Buckles, V., Fagan, A. M., Ladenson, J. H., … Holtzman, D. M. (2015). Cerebrospinal Fluid Markers of Neurodegeneration and Rates of Brain Atrophy in Early Alzheimer Disease. JAMA Neurology, 63110, 1–10. Available at: http://doi.org/10.1001/jamaneurol.2015.0202

Yanamandra, K., Jiang, H., Mahan, T. E., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2015). Anti-tau antibody reduces insoluble tau and decreases brain atrophy. Annals of Clinical and Translational Neurology, 2(3), 278–288. Available at:http://doi.org/10.1002/acn3.176

Snyder HM, Carrillo MC, Grodstein F, Henriksen K, Jeromin A, Lovestone S, Mielke MM, O’Bryant S, Sarasa M, Sjøgren M, Soares H, Teeling J, Trushina E, Ward M, West T, Bain LJ, Shineman DW, Weiner M, Fillit HM (2014) Developing novel blood-based biomarkers for Alzheimer’s disease. Alzheimers Dement 10:109–114 Available at:http://www.ncbi.nlm.nih.gov/pubmed/24365657.

Sheline YI, West T, Yarasheski K, Swarm R, Jasielec MS, Fisher JR, Ficker WD, Yan P, Xiong C, Frederiksen C, Grzelak M V, Chott R, Bateman RJ, Morris JC, Mintun M a, Lee J-M, Cirrito JR (2014) An antidepressant decreases CSF Aβ production in healthy individuals and in transgenic AD mice. Sci Transl Med 6:236re4 Available at:http://www.ncbi.nlm.nih.gov/pubmed/24828079.

  • SILKTM methodology was used to study the effect of antidepressant Citalopram on Aβ production and concentrations in CSF. It was found that Aβ production in CSF was slowed by 37% in the citalopram group compared to placebo

Roberts KF, Elbert DL, Kasten TP, Patterson BW, Sigurdson WC, Connors RE, Ovod V, Munsell LY, Mawuenyega KG, Miller-Thomas MM, Moran CJ, Cross DT, Derdeyn CP, Bateman RJ (2014) Amyloid-β efflux from the CNS into the plasma. Ann Neurol 010 Available at:http://www.ncbi.nlm.nih.gov/pubmed/25205593.

Fagan a. M et al. (2014) Longitudinal Change in CSF Biomarkers in Autosomal-Dominant Alzheimer’s Disease. Sci Transl Med 6:226ra30–ra226ra30 Available at:http://stm.sciencemag.org/cgi/doi/10.1126/scitranslmed.3007901.

Elbert DL, Patterson BW, Bateman RJ (2014) Analysis of a compartmental model of amyloid beta production, irreversible loss and exchange in humans. Math Biosci Available at:http://linkinghub.elsevier.com/retrieve/pii/S0025556414002375.

  • In-depth description of the multicompartment model described in Potter et. al. (2013)

Dubois B et al. (2014) Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 13:614–629 Available at:http://www.ncbi.nlm.nih.gov/pubmed/24849862.

Potter R, Patterson BW, Elbert DL, Ovod V, Kasten T, Sigurdson W, Mawuenyega K, Blazey T, Goate A, Chott R, Yarasheski KE, Holtzman DM, Morris JC, Benzinger TLS, Bateman RJ (2013) Increased in vivo amyloid-β42 production, exchange, and loss in presenilin mutation carriers. Sci Transl Med 5:189ra77 Available at:http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3838868&tool=pmcentrez&rendertype=abstract.

  • SILKTM methodology was used to measure fractional turnover rates of Abeta38, Abeta40 and Abeta42 in PSEN mutation carriers and noncarriers. Based on the results a multi-compartment model was developed to describe Abeta isoform kinetics

Wildsmith KR, Basak JM, Patterson BW, Pyatkivskyy Y, Kim J, Yarasheski KE, Wang JX, Mawuenyega KG, Jiang H, Parsadanian M, Yoon H, Kasten T, Sigurdson WC, Xiong C, Goate A, Holtzman DM, Bateman RJ (2012) In vivo human apolipoprotein E isoform fractional turnover rates in the CNS. PLoS One 7:e38013 Available at:http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3366983&tool=pmcentrez&rendertype=abstract.

  • SILKTM methodology was employed to measure fractional turnover rates of ApoE isoforms in 18 cognitively normal adults

Roh JH, Huang Y, Bero a. W, Kasten T, Stewart FR, Bateman RJ, Holtzman DM (2012) Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of -Amyloid in Mice with Alzheimer’s Disease Pathology. Sci Transl Med 4:150ra122–ra150ra122 Available at:http://stm.sciencemag.org/cgi/doi/10.1126/scitranslmed.3004291.

Huang Y, Potter R, Sigurdson W, Kasten T, Connors R, Morris JC, Benzinger T, Mintun M, Ashwood T, Ferm M, Budd SL, Bateman RJ (2012) β-Amyloid Dynamics in Human Plasma. Arch Neurol:1–7 Available at:http://www.ncbi.nlm.nih.gov/pubmed/22964799.

  • Hourly measurements with ELISA showed that plasma Abeta, like CSF, demonstrates a circadian pattern that is reduced in amplitude with increase in age but is unaffected by amyloid deposition. There is no correlation between plasma and CSF Abeta concentrations.

Esparza TJ, Zhao H, Cirrito JR, Cairns NJ, Bateman RJ, Holtzman DM, Brody DL (2012) Amyloid-beta oligomerization in alzheimer dementia vs. high pathology controls. Ann Neurol Available at:http://doi.wiley.com/10.1002/ana.23748.

Castellano JM, Deane R, Gottesdiener AJ, Verghese PB, Stewart FR, West T, Paoletti AC, Kasper TR, DeMattos RB, Zlokovic B V., Holtzman DM (2012) Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood Aβ clearance in a mouse model of β-amyloidosis. Proc Natl Acad Sci U S A 109:15502–15507 Available at:http://www.pnas.org/cgi/doi/10.1073/pnas.1206446109.

  • This research paper showed that LDLR overexpression enhances brain-to-blood Abeta transport and suggest that LDLR regulation may serve as a useful therapeutic avenue in targeting Abeta clearance from the brain

Bateman RJ et al. (2012) Clinical and Biomarker Changes in Dominantly Inherited Alzheimer’s Disease. N Engl J Med:120711140017009 Available at:http://www.nejm.org/doi/abs/10.1056/NEJMoa1202753.

Basak JM, Kim J, Pyatkivskyy Y, Wildsmith KR, Jiang H, Parsadanian M, Patterson BW, Bateman RJ, Holtzman DM (2012) Measurement of apolipoprotein E and amyloid beta clearance rates in the mouse brain using bolus stable isotope labeling. Mol Neurodegener 7:14 Available at:http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3405485&tool=pmcentrez&rendertype=abstract.

  • SILKTM technology was adapted to be used in mouse to measure the clearance rates of brain proteins

Huang Y, Potter R, Sigurdson W, Santacruz A, Shih S, Ju Y-E, Kasten T, Morris JC, Mintun M, Duntley S, Bateman RJ (2011) Effects of Age and Amyloid Deposition on A{beta} Dynamics in the Human Central Nervous System. Arch Neurol Available at:http://www.ncbi.nlm.nih.gov/pubmed/21911660.

  • Hourly measurements with ELISA showed a reduction in the linear increase in the Abeta levels in CSF samples that is associated with amyloid deposition and a decreased CSF Abeta diurnal pattern associated with increasing age disrupt the normal physiology of Abeta dynamics and may contribute to AD

Castellano JM, Kim J, Stewart FR, Jiang H, DeMattos RB, Patterson BW, Fagan a. M, Morris JC, Mawuenyega KG, Cruchaga C, Goate a. M, Bales KR, Paul SM, Bateman RJ, Holtzman DM (2011) Human apoE Isoforms Differentially Regulate Brain Amyloid- Peptide Clearance. Sci Transl Med 3:89ra57–ra89ra57 Available at:http://stm.sciencemag.org/cgi/doi/10.1126/scitranslmed.3002156.

Bateman RJ, Aisen PS, De Strooper B, Fox NC, Lemere C, Ringman J, Salloway S, Sperling RA, Windisch M, Xiong C (2011) Autosomal-dominant Alzheimer’s disease: a review and proposal for the prevention of Alzheimer’s disease. Alzheimers Res Ther 2:35 Available at:http://alzres.com/content/2/6/35/abstract.

Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC, Yarasheski KE, Bateman RJ (2010a) Decreased Clearance of CNS b-Amyloid in Alzheimer’s Disease – SOM. Science (80- ) Available at:http://www.sciencemag.org/cgi/doi/10.1126/science.1197623.

  • Result from a SILKTM study in 12 AD and 12 control subjects suggested that there is imbalance in Abeta40 and Abeta42 production and clearance ratio in AD subjects

Cook JJ, Wildsmith KR, Gilberto DB, Holahan MA, Kinney GG, Mathers PD, Michener MS, Price EA, Shearman MS, Simon AJ, Wang JX, Wu G, Yarasheski KE, Bateman RJ (2010) Acute gamma-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-beta production to alternative APP fragments without amyloid-beta rebound. J Neurosci 30:6743–6750 Available at:http://www.ncbi.nlm.nih.gov/pubmed/20463236.

  • SILKTM technology was adapted to be used in non-human primates and the effect of Merk’s gamma-secretase inhibitor on A production was studied

Wildsmith KR, Han B, Bateman RJ (2009) Method for the simultaneous quantitation of apolipoprotein E isoforms using tandem mass spectrometry. Anal Biochem 395:116–118 Available at:http://dx.doi.org/10.1016/j.ab.2009.07.049.

  • Use of SILKTM to measure apoE metabolism

Kang J-E, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, Fujiki N, Nishino S, Holtzman DM (2009) Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science 326:1005–1007 Available at:http://www.ncbi.nlm.nih.gov/pubmed/19779148.

Bateman RJ, Siemers ER, Mawuenyega KG, Wen G, Browning KR, Sigurdson WC, Yarasheski KE, Friedrich SW, Demattos RB, May PC, Paul SM, Holtzman DM (2009) A gamma-secretase inhibitor decreases amyloid-beta production in the central nervous system. Ann Neurol 66:48–54 Available at:http://www.ncbi.nlm.nih.gov/pubmed/19360898.

  • Using SILKTM methogology, the authors showed that Eli Lilly’s gamma-secretase inhibitor LY450139 significantly decreased the production of CNS Abeta in a dose-dependent fashion

Elbert DL, Mawuenyega KG, Scott EA, Wildsmith KR, Bateman RJ (2008) Stable isotope labeling tandem mass spectrometry (SILT): integration with peptide identification and extension to data-dependent scans. J Proteome Res 7:4546–4556 Available at:http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2707264&tool=pmcentrez&rendertype=abstract.

  • This research article describes method improvement on SILKTM technology

Bateman RJ, Klunk WE (2008) Measuring Target Effect of Proposed Disease-Modifying Therapies in Alzheimer’s Disease. Society 5:381–390.

  • A review article that discusses measurement of Abeta production and clearance using SILKTM methodology could be used as a biomarker for AD therapeutics

Bateman RJ, Wen G, Morris JC, Holtzman DM (2007b) Fluctuations of CSF amyloid-beta levels: implications for a diagnostic and therapeutic biomarker. Neurology 68:666–669 Available at:http://www.ncbi.nlm.nih.gov/pubmed/17325273.

  • Fluctuation of CSF amyloid-beta levels were assessed in 15 cognitively normal subjects with ELISA

Bateman RJ, Munsell LY, Chen X, Holtzman DM, Yarasheski KE (2007a) Stable isotope labeling tandem mass spectrometry (SILT) to quantify protein production and clearance rates. J Am Soc Mass Spectrom 18:997–1006 Available at:http://www.ncbi.nlm.nih.gov/pubmed/17383190.

  • A further validation of SILKTM technology: Abeta synthesis and clearance rate were studied in a middle-aged subject

Bateman RJ, Eidelberg D (2007) Testing a test for Alzheimer disease. Neurology 68:482–483 Available at:http://www.ncbi.nlm.nih.gov/pubmed/17296912.

Bateman RJ, Munsell LY, Morris JC, Swarm R, Yarasheski KE, Holtzman DM (2006) Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat Med 12:856–861 Available at:http://www.ncbi.nlm.nih.gov/pubmed/16799555.

  • The very first publication describing SILKTM technology: Abeta synthesis and clearance rate were studied in ten young healthy subject