Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE

Nature Communications

Volumn 6, Issue , 2015, Pages

  Ayton, Scott ^a   Faux, Noel G ^a,b   Bush, Ashley I ^a,b   Weiner, Michael W ^c   Aisen, Paul ^d   Petersen, Ronald ^e   Jack, Clifford R ^e   Jagust, William ^f   Trojanowki, John Q ^g   Toga, Arthur W ^h   Beckett, Laurel ⁱ   Green, Robert C ^j   Saykin, Andrew J ^k   Morris, John ^l   Shaw, Leslie M ^g   Khachaturian, Zaven ^d,m   Sorensen, Greg ⁿ   Kuller, Lew ^o   Raichle, Marc ^l   Paul, Steven ^p   Davies, Peter ^q   Fillit, Howard ^r   Hefti, Franz ^s   Holtzman, Davie ^l   Mesulam, M Marcel ^t   Potter, William ^u   Snyder, Peter ^v   Schwartz, Adam ^w   Montine, Tom ^x   Thomas, Ronald G ^d   Donohue, Michael ^d   Walter, Sarah ^d   Gessert, Devon ^d   Sather, Tamie ^d   Jiminez, Gus ^d   Harvey, Danielle ⁱ   Bernstein, Matthew ^e   Fox, Nick ^y   Thompson, Paul ^z   Schuff, Norbert ^c,i   Borowski, Bret ^e   Gunter, Jeff ^e   Senjem, Matt ^e   Vemuri, Prashanthi ^e   Jones, David ^e   Kantarci, Kejal ^e   Ward, Chad ^e   Koeppe, Robert A ^aa   Foster, Norm ^ab   Reiman, Eric M ^ac   Chen, Kewei ^ac   Mathis, Chet ^o   Landau, Susan ^f   Cairns, Nigel J ^l   Householder, Erin ^l   Taylor Reinwald, Lisa ^l   Lee, Virginia ^g   Korecka, Magdalena ^g   Figurski, Michal ^g   Crawford, Karen ^h   Neu, Scott ^h   Foroud, Tatiana M ^k   Potkin, Steven ^ad   Shen, Li ^k   Faber, Kelley ^k   Kim, Sungeun ^k   Nho, Kwangsik ^k   Thal, Leon ^d   Buckholtz, Neil ^ae   Albert, Marylyn ^af   Frank, Richard ^ag   Hsiao, John ^ae   Kaye, Jeffrey ^ah   Quinn, Joseph ^ah   Lind, Betty ^ah   Carter, Raina ^ah   Dolen, Sara ^ah   Schneider, Lon S ^h   Pawluczyk, Sonia ^h   Beccera, Mauricio ^h   Teodoro, Liberty ^h   Spann, Bryan M ^h   Brewer, James ^d   Vanderswag, Helen ^d   Fleisher, Adam ^d,ac   Heidebrink, Judith L ^aa   Lord, Joanne L ^aa   Mason, Sara S ^e   Albers, Colleen S ^e   Knopman, David ^e   Johnson, Kris ^e   Doody, Rachelle S ^ai   Villanueva Meyer, Javier ^ai   Chowdhury, Munir ^ai   Rountree, Susan ^ai   Dang, Mimi ^ai   Stern, Yaakov ^ai   Honig, Lawrence S ^ai   Bell, Karen L ^ai   Ances, Beau ^l   Carroll, Maria ^l   Leon, Sue ^l   Mintun, Mark A ^l   Schneider, Stacy ^l   Oliver, Angela ^l   Marson, Daniel ^aj   Griffith, Randall ^aj   Clark, David ^aj   Geldmacher, David ^aj   Brockington, John ^aj   Roberson, Erik ^aj   Grossman, Hillel ^ak   Mitsis, Effie ^ak   De Toledo Morrell, Leyla ^al   Shah, Raj C ^al   Duara, Ranjan ^am   Varon, Daniel ^am   Greig, Maria T ^am   Roberts, Peggy ^am   Albert, Marilyn ^af   Onyike, Chiadi ^af   D'Agostino, Daniel ^af   Kielb, Stephanie ^af   Galvin, James E ^an   Cerbone, Brittany ^an   Michel, Christina A ^an   Rusinek, Henry ^an   De Leon, Mony J ^an   Glodzik, Lidia ^an   De Santi, Susan ^an   Doraiswamy, P Murali ^ao   Petrella, Jeffrey R ^ao   Wong, Terence Z ^ao   Arnold, Steven E ^g   Karlawish, Jason H ^g   Wolk, David ^g   Smith, Charles D ^ap   Jicha, Greg ^ap   Hardy, Peter ^ap   Sinha, Partha ^ap   Oates, Elizabeth ^ap   Conrad, Gary ^ap   Lopez, Oscar L ^o   Oakley, Mary Ann ^o   Simpson, Donna M ^af   Porsteinsson, Anton P ^aq   Goldstein, Bonnie S ^aq   Martin, Kim ^aq   Makino, Kelly M ^aq   Ismail, M Saleem ^aq   Brand, Connie ^aq   Mulnard, Ruth A ^ad   Thai, Gaby ^ad   Mc Adams Ortiz, Catherine ^ad   Womack, Kyle ^ar   Mathews, Dana ^ar   Quiceno, Mary ^ar   Diaz Arrastia, Ramon ^ar   King, Richard ^ar   Weiner, Myron ^ar   Martin Cook, Kristen ^ar   DeVous, Michael ^ar   Levey, Allan I ^as   Lah, James J ^as   Cellar, Janet S ^as   Burns, Jeffrey M ^at   Anderson, Heather S ^at   Swerdlow, Russell H ^at   Apostolova, Liana ^z   Tingus, Kathleen ^z   Woo, Ellen ^z   Silverman, Daniel H S ^z   Lu, Po H ^z   Bartzokis, George ^z   Graff Radford, Neill R ^e   Parfitt, Francine ^e   Kendall, Tracy ^e   Johnson, Heather ^e   Farlow, Martin R ^k   Hake, Ann Marie ^k   Matthews, Brandy R ^k   Herring, Scott ^k   Hunt, Cynthia ^k   Van Dyck, Christopher H ^au   Carson, Richard E ^au   MacAvoy, Martha G ^au   Chertkow, Howard ^av   Bergman, Howard ^av   Hosein, Chris ^av   Black, Sandra ^aw   Stefanovic, Bojana ^aw   Caldwell, Curtis ^aw   Hsiung, Ging Yuek Robin ^ax   Feldman, Howard ^ax   Mudge, Benita ^ax   Assaly, Michele ^ax   Kertesz, Andrew ^ay,br   Rogers, John ^ay,br   Bernick, Charles ^ay   Munic, Donna ^ay   Kerwin, Diana ^t   Mesulam, Marek Marsel ^t   Lipowski, Kristine ^t   Wu, Chuang Kuo ^t   Johnson, Nancy ^t   Sadowsky, Carl ^az   Martinez, Walter ^az   Villena, Teresa ^az   Turner, Raymond Scott ^ba   Johnson, Kathleen ^ba   Reynolds, Brigid ^ba   Sperling, Reisa A ^j   Johnson, Keith A ^j   Marshall, Gad ^j   Frey, Meghan ^j   Lane, Barton ^j   Rosen, Allyson ^j   Tinklenberg, Jared ^j   Sabbagh, Marwan N ^bb   Belden, Christine M ^bb   Jacobson, Sandra A ^bb   Sirrel, Sherye A ^bb   Kowall, Neil ^bc   Killiany, Ronald ^bc   Budson, Andrew E ^bc   Norbash, Alexander ^bc   Johnson, Patricia Lynn ^bc   Allard, Joanne ^bd   Lerner, Alan ^be   Ogrocki, Paula ^be   Hudson, Leon ^be   Fletcher, Evan ⁱ   Carmichael, Owen ⁱ   Olichney, John ⁱ   DeCarli, Charles ⁱ   Kittur, Smita ^bf   Borrie, Michael ^bg   Lee, T Y ^bg   Bartha, Rob ^bg   Johnson, Sterling ^bh   Asthana, Sanjay ^bh   Carlsson, Cynthia M ^bh   Potkin, Steven G ^aa   Preda, Adrian ^aa   Nguyen, Dana ^aa   Tariot, Pierre ^ac   Reeder, Stephanie ^ac   Bates, Vernice ^bi   Capote, Horacio ^bi   Rainka, Michelle ^bi   Scharre, Douglas W ^bj   Kataki, Maria ^bj   Adeli, Anahita ^bj   Zimmerman, Earl A ^bk   Celmins, Dzintra ^bk   Brown, Alice D ^bk   Pearlson, Godfrey D ^bl   Blank, Karen ^bl   Anderson, Karen ^bl   Santulli, Robert B ^bm   Kitzmiller, Tamar J ^bm   Schwartz, Eben S ^bm   Sink, Kaycee M ^bn   Williamson, Jeff D ^bn   Garg, Pradeep ^bn   Watkins, Franklin ^bn   Ott, Brian R ^bo   Querfurth, Henry ^bo   Tremont, Geoffrey ^bo   Salloway, Stephen ^bp   Malloy, Paul ^bp   Correia, Stephen ^bp   Rosen, Howard J ^c   Miller, Bruce L ^c   Mintzer, Jacobo ^bq   Spicer, Kenneth ^bq   Bachman, David ^bq   Finger, Elizabether ^br   Pasternak, Stephen ^br   Rachinsky, Irina ^br   Drost, Dick ^br   Pomara, Nunzio ^bs   Hernando, Raymundo ^bs   Sarrael, Antero ^bs   Schultz, Susan K ^bt   Boles Ponto, Laura L ^bt   Shim, Hyungsub ^bt   Smith, Karen Elizabeth ^bt   Relkin, Norman ^p   Chaing, Gloria ^p   Raudin, Lisa ^m,p   Smith, Amanda ^bu   Fargher, Kristin ^bu   Raj, Balebail Ashok ^bu   Neylan, Thomas ^c   Grafman, Jordan ^t   Davis, Melissa ^d   Morrison, Rosemary ^d   Hayes, Jacqueline ^c   Finley, Shannon ^c   Friedl, Karl ^m   Fleischman, Debra ^al   Arfanakis, Konstantinos ^al   James, Olga ^ao   Massoglia, Dino ^bq   Fruehling, J Jay ^bh   Harding, Sandra ^bh   Peskind, Elaine R ^x   Petrie, Eric C ^bj   Li, Gail ^bj   Yesavage, Jerome A ^bv   Taylor, Joy L ^bv   Furst, Ansgar J ^bv   more..

^a UNIVERSITY OF MELBOURNE   (Australia)

^b Department of Civil and Environmental Engineering   (Australia)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e MAYO CLINIC   (United States)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g UNIVERSITY OF PENNSYLVANIA   (United States)

^h Dept of Physics   (United States)

ⁱ UNIVERSITY OF CALIFORNIA   (United States)

^j BRIGHAM AND WOMEN S HOSPITAL   (United States)

^k INDIANA UNIVERSITY   (United States)

^l WASHINGTON UNIVERSITY   (United States)

^m Prevent Alzheimer's Disease 2020 ^*  (United States)

ⁿ SIEMENS AG   (Germany)

^o UNIVERSITY OF PITTSBURGH   (United States)

^p Department of Obstetrics Gynecology   (United States)

^q ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^r AD Drug Discovery Foundation   (United States)

^s Acumen Pharmaceuticals Inc   (United States)

^t NORTHWESTERN UNIVERSITY   (United States)

^u NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^v BROWN UNIVERSITY   (United States)

^w ELI LILLY   (United States)

^x UNIVERSITY OF WASHINGTON   (United States)

^y UNIVERSITY OF LONDON   (United Kingdom)

^z UNIVERSITY OF CALIFORNIA   (United States)

^aa UNIVERSITY OF MICHIGAN   (United States)

^ab UNIVERSITY OF UTAH   (United States)

^ac BANNER ALZHEIMER S INSTITUTE   (United States)

^ad UNIVERSITY OF CALIFORNIA   (United States)

^ae NATIONAL INSTITUTE ON AGING   (United States)

^af JOHNS HOPKINS UNIVERSITY   (United States)

^ag Richard Frank Consulting   (United States)

^ah OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^ai BAYLOR COLLEGE OF MEDICINE   (United States)

^aj UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^ak MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^al RUSH UNIVERSITY MEDICAL CENTER   (United States)

^am Wien Center   (United States)

^an NEW YORK UNIVERSITY   (United States)

^ao DUKE UNIVERSITY MEDICAL CENTER   (United States)

^ap UNIVERSITY OF KENTUCKY   (United States)

^aq UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^ar UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^as EMORY UNIVERSITY   (United States)

^at UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

^au YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^av MCGILL UNIVERSITY   (Canada)

^aw SUNNYBROOK RESEARCH INSTITUTE   (Canada)

^ax UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^ay UBC Clinic for AD and Related Disorders ^*  (United States)

^az Premiere Research Institute   (United States)

^ba GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

^bb SUN HEALTH RESEARCH INSTITUTE   (United States)

^bc BOSTON UNIVERSITY   (United States)

^bd HOWARD UNIVERSITY   (United States)

^be CASE WESTERN RESERVE UNIVERSITY   (United States)

^bf Neurological Care of CNY   (United States)

^bg Department of Medicine   (Canada)

^bh University of Wisconsin   (United States)

^bi Dent Neurologic Institute   (United States)

^bj OHIO STATE UNIVERSITY   (United States)

^bk ALBANY MEDICAL COLLEGE   (United States)

^bl HARTFORD HOSPITAL   (United States)

^bm DARTMOUTH HITCHCOCK MEDICAL CENTER   (United States)

^bn WAKE FOREST UNIVERSITY HEALTH SCIENCES   (United States)

^bo RHODE ISLAND HOSPITAL   (United States)

^bp BUTLER HOSPITAL   (United States)

^bq Medical University of South Carolina   (United States)

^br St Joseph's Health Care   (Australia)

^bs Nathan Kline Institute for Psychiatric Research   (United States)

^bt UNIVERSITY OF IOWA   (United States)

^bu UNIVERSITY OF SOUTH FLORIDA   (United States)

^bv STANFORD UNIVERSITY   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN[1-42]; APOLIPOPROTEIN E; APOLIPOPROTEIN E EPSILON 4; FERRITIN; TAU PROTEIN; UNCLASSIFIED DRUG; IRON;

NERVOUS SYSTEM DISORDER;

AGED; ALLELE; ALZHEIMER DISEASE; ARTICLE; BRAIN ATROPHY; CEREBROSPINAL FLUID; COGNITION; CONTROLLED STUDY; FEMALE; HUMAN; MAJOR CLINICAL STUDY; MALE; MILD COGNITIVE IMPAIRMENT; OUTCOME ASSESSMENT; ATROPHY; BRAIN; COGNITIVE DEFECT; COHORT ANALYSIS; FACTUAL DATABASE; GENE EXPRESSION REGULATION; GENETICS; GENOTYPE; LONGITUDINAL STUDY; METABOLISM; MIDDLE AGED; NUCLEAR MAGNETIC RESONANCE IMAGING; RISK FACTOR; TREATMENT OUTCOME; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; APOLIPOPROTEINS E; ATROPHY; BRAIN; COGNITION; COGNITION DISORDERS; COHORT STUDIES; DATABASES, FACTUAL; FEMALE; FERRITINS; GENE EXPRESSION REGULATION; GENOTYPE; HUMANS; IRON; LONGITUDINAL STUDIES; MAGNETIC RESONANCE IMAGING; MALE; MIDDLE AGED; RISK FACTORS; TREATMENT OUTCOME;

EID: 84930225631     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms7760     Document Type: Article

References (48)

1. van Rooden, S. et al. 7T T2-weighted magnetic resonance imaging reveals cortical phase differences between early-and late-onset Alzheimer's disease. Neurobiol. Aging 36, 20-26 (2014).
2. Smith, M. A., Harris, P. L., Sayre, L. M. & Perry, G. Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc. Natl Acad. Sci. USA 94, 9866-9868 (1997).
3. Crapper McLachlan, D. R. et al. Intramuscular desferrioxamine in patients with Alzheimer's disease. Lancet 337, 1304-1308 (1991).
4. Lei, P. et al. Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat. Med. 18, 291-295 (2012).
5. Jellinger, K., Paulus, W., Grundke-Iqbal, I., Riederer, P. & Youdim, M. B. Brain iron and ferritin in Parkinson's and Alzheimer's diseases. J. Neural Transm. Park. Dis. Dement. Sect. 2, 327-340 (1990).
6. Connor, J. R., Menzies, S. L., St Martin, S. M. & Mufson, E. J. A histochemical study of iron, transferrin, and ferritin in Alzheimer's diseased brains. J. Neurosci. Res. 31, 75-83 (1992).
7. Bartzokis, G., Tishler, T. A., Shin, I. S., Lu, P. H. & Cummings, J. L. Brain ferritin iron as a risk factor for age at onset in neurodegenerative diseases. Ann. N. Y. Acad. Sci. 1012, 224-236 (2004).
8. Quintana, C. et al. Study of the localization of iron, ferritin, and hemosiderin in Alzheimer's disease hippocampus by analytical microscopy at the subcellular level. J. Struct. Biol. 153, 42-54 (2006).
9. Hansen, T. M., Nielsen, H., Bernth, N. & Moos, T. Expression of ferritin protein and subunit mRNAs in normal and iron deficient rat brain. Brain Res. Mol. Brain Res. 65, 186-197 (1999).
10. Malecki, E. A., Cable, E. E., Isom, H. C. & Connor, J. R. The lipophilic iron compound TMH-ferrocene [(3,5,5-trimethylhexanoyl)ferrocene] increases iron concentrations, neuronal L-ferritin, and heme oxygenase in brains of BALB/c mice. Biol. Trace Elem. Res. 86, 73-84 (2002).
11. Zhang, X., Surguladze, N., Slagle-Webb, B., Cozzi, A. & Connor, J. R. Cellular iron status influences the functional relationship between microglia and oligodendrocytes. Glia 54, 795-804 (2006).
12. Earley, C. J. et al. Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology 54, 1698-1700 (2000).
13. Kuiper, M. A., Mulder, C., van Kamp, G. J., Scheltens, P. & Wolters, E. C. Cerebrospinal fluid ferritin levels of patients with Parkinson's disease, Alzheimer's disease, and multiple system atrophy. J. Neural Transm. Park. Dis. Dement. Sect. 7, 109-114 (1994).
14. Craig-Schapiro, R. et al. Multiplexed immunoassay panel identifies novel CSF biomarkers for Alzheimer's disease diagnosis and prognosis. PloS ONE 6, e18850 (2011).
15. Paterson, R. W. et al. Cerebrospinal fluid markers including trefoil factor 3 are associated with neurodegeneration in amyloid-positive individuals. Transl. Psychiatry 4, e419 (2014).
16. Mattsson, N. et al. Effects of cerebrospinal fluid proteins on brain atrophy rates in cognitively healthy older adults. Neurobiol. Aging 35, 614-622 (2014).
17. Mattsson, N. et al. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 302, 385-393 (2009).
18. Corder, E. H. et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261, 921-923 (1993).
19. Cruchaga, C. et al. Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease. Hum. Mol. Genet. 21, 4558-4571 (2012).
20. Martinez-Morillo, E. et al. Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer's disease patients and controls. Acta Neuropathol. 127, 633-643 (2014).
21. Toledo, J. B. et al. CSF Apo-E levels associate with cognitive decline and MRI changes. Acta Neuropathol. 127, 621-632 (2014).
22. Kester, M. I. et al. CSF biomarkers predict rate of cognitive decline in Alzheimer disease. Neurology 73, 1353-1358 (2009).
23. Estevez-Gonzalez, A., Kulisevsky, J., Boltes, A., Otermin, P. & Garcia-Sanchez, C. Rey verbal learning test is a useful tool for differential diagnosis in the preclinical phase of Alzheimer's disease: comparison with mild cognitive impairment and normal aging. Int. J. Geriatr. Psychiatry 18, 1021-1028 (2003).
24. Mattsson, N. et al. CSF protein biomarkers predicting longitudinal reduction of CSF beta-amyloid42 in cognitively healthy elders. Transl. Psychiatry 3, e293 (2013).
25. Apostolova, L. G. et al. 3D PIB and CSF biomarker associations with hippocampal atrophy in ADNI subjects. Neurobiol. Aging 31, 1284-1303 (2010).
26. Devos, D. et al. Targeting chelatable iron as a therapeutic modality in Parkinson's disease. Antioxid. Redox Signal. 21, 195-210 (2014).
27. Duce, J. A. et al. Iron-export ferroxidase activity of beta-amyloid precursor protein is inhibited by zinc in Alzheimer's disease. Cell 142, 857-867 (2010).
28. Christensen, D. Z., Schneider-Axmann, T., Lucassen, P. J., Bayer, T. A. & Wirths, O. Accumulation of intraneuronal Abeta correlates with ApoE4 genotype. Acta Neuropathol. 119, 555-566 (2010).
29. Huang, X. et al. The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry 38, 7609-7616 (1999).
30. Yamamoto, A. et al. Iron (III) induces aggregation of hyperphosphorylated tau and its reduction to iron (II) reverses the aggregation: implications in the formation of neurofibrillary tangles of Alzheimer's disease. J. Neurochem. 82, 1137-1147 (2002).
31. Tofaris, G. K., Revesz, T., Jacques, T. S., Papacostas, S. & Chataway, J. Adultonset neurodegeneration with brain iron accumulation and cortical alphasynuclein and tau pathology: a distinct clinicopathological entity. Arch. Neurol. 64, 280-282 (2007).
32. Kondziella, D. & Zetterberg, H. Hyperphosphorylation of tau protein in superficial CNS siderosis. J. Neurol. Sci. 273, 130-132 (2008).
33. Lee, J. Y. et al. Apolipoprotein E ablation decreases synaptic vesicular zinc in the brain. Biometals 23, 1085-1095 (2010).
34. Lomnitski, L., Nyska, A., Shohami, E., Chen, Y. & Michaelson, D. M. Increased levels of intracellular iron in the brains of A poE-deficient mice with closed head injury. Exp. Toxicol. Pathol. 52, 177-183 (2000).
35. Yuan, X. M., Li, W., Baird, S. K., Carlsson, M. & Melefors, O. Secretion of ferritin by iron-laden macrophages and influence of lipoproteins. Free Radic. Res. 38, 1133-1142 (2004).
36. Dong, L. M. et al. Human apolipoprotein E. Role of arginine 61 in mediating the lipoprotein preferences of the E3 and E4 isoforms. J. Biol. Chem. 269, 22358-22365 (1994).
37. Ali-Rahmani, F., Schengrund, C. L. & Connor, J. R. HFE gene variants, iron, and lipids: a novel connection in Alzheimer's disease. Front. Pharmacol. 5, 165 (2014).
38. Weiner, M. W. et al. The Alzheimer's Disease Neuroimaging Initiative: a review of papers published since its inception. Alzheimer's Dement. 8, S1-68 (2012).
39. McKhann, G. et al. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34, 939-944 (1984).
40. Shaw, L. M. et al. Qualification of the analytical and clinical performance of CSF biomarker analyses in ADNI. Acta Neuropathol. 121, 597-609 (2011).
41. Shaw, L. M. et al. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann. Neurol. 65, 403-413 (2009).
42. Jack, Jr. C. R. et al. The Alzheimer's disease neuroimaging initiative (ADNI): MRI methods. J. Magn. Reson. Imag. 27, 685-691 (2008).
43. Team, R.C. R. A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2014).
44. Wickham, H. Ggplot2: Elegant Graphics for Data Analysis (Springer New York, 2009).
45. Pinheiro, J., Bates, D., DebRoy, S., Sarkar, D. & Team, R. C. nlme: Linear and Nonlinear Mixed Effects Models (2014).
46. Fox, J. & Weisberg, S. An R Companion to Applied Regression (Sage, 2011).
47. Fellows, I. Deducer: a data analysis GUI for R. J. Stat. Softw. 48, 1-15 (2012).
48. Kim, Y. O., Kang, J. S., Youm, M. H. & Jong Woo, Y. Diagnostic capability of CSF ferritin in children with meningitis. Pediatr. Neurol. 28, 271-276 (2003).