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@ARTICLE{Toledo:138121,
author = {Toledo, Jon B and Zetterberg, Henrik and van Harten,
Argonde C and Glodzik, Lidia and Martinez-Lage, Pablo and
Bocchio-Chiavetto, Luisella and Rami, Lorena and Hansson,
Oskar and Sperling, Reisa and Engelborghs, Sebastiaan and
Osorio, Ricardo S and Vanderstichele, Hugo and Vandijck,
Manu and Hampel, Harald and Teipel, Stefan and Moghekar,
Abhay and Albert, Marilyn and Hu, William T and Monge
Argilés, Jose A and Gorostidi, Ana and Teunissen, Charlotte
E and De Deyn, Peter P and Hyman, Bradley T and Molinuevo,
Jose L and Frisoni, Giovanni B and Linazasoro, Gurutz and de
Leon, Mony J and van der Flier, Wiesje M and Scheltens,
Philip and Blennow, Kaj and Shaw, Leslie M and Trojanowski,
John Q and Initiative, Alzheimer’s Disease Neuroimaging
and Weiner, Michael W and Aisen, Paul and Weiner, Michael
and Aisen, Paul and Petersen, Ronald and Jack, Clifford R
and Jagust, William and Trojanowki, John Q and Toga, Arthur
W and Beckett, Laurel and Green, Robert C and Saykin, Andrew
J and Morris, John and Shaw, Leslie M and Khachaturian,
Zaven and Sorensen, Greg and Carrillo, Maria and Kuller, Lew
and Raichle, Marc and Paul, Steven and Davies, Peter and
Fillit, Howard and Hefti, Franz and Holtzman, Davie and
Mesulam, M Marcel and Potter, William and Snyder, Peter and
Schwartz, Adam and Green, Robert C and Montine, Tom and
Petersen, Ronald and Aisen, Paul and Thomas, Ronald G and
Donohue, Michael and Walter, Sarah and Gessert, Devon and
Sather, Tamie and Jiminez, Gus and Balasubramanian, Archana
B and Mason, Jennifer and Sim, Iris and Beckett, Laurel and
Harvey, Danielle and Donohue, Michael and Jack, Clifford R
and Bernstein, Matthew and Fox, Nick and Thompson, Paul and
Schuff, Norbert and DeCArli, Charles and Borowski, Bret and
Gunter, Jeff and Senjem, Matt and Vemuri, Prashanthi and
Jones, David and Kantarci, Kejal and Ward, Chad and Jagust,
William and Koeppe, Robert A and Foster, Norm and Reiman,
Eric M and Chen, Kewei and Mathis, Chet and Landau, Susan
and Morris, John C and Cairns, Nigel J and Householder, Erin
and Taylor-Reinwald, Lisa and Shaw, Leslie M and Trojanowki,
John Q and Lee, Virginia and Korecka, Magdalena and
Figurski, Michal and Toga, Arthur W and Crawford, Karen and
Neu, Scott and Saykin, Andrew J and Foroud, Tatiana M and
Potkin, Steven and Shen, Li and Faber, Kelley and Kim,
Sungeun and Nho, Kwangsik and Weiner, Michael W and Thal,
Lean and Khachaturian, Zaven and Thal, Leon and Buckholtz,
Neil and Weiner, Michael W and Snyder, Peter J and Potter,
William and Paul, Steven and Albert, Marylyn and Frank,
Richard and Khachaturian, Zaven and Hsiao, John and Kaye,
Jeffrey and Quinn, Joseph and Silbert, Lisa and Lind, Betty
and Carter, Raina and Dolen, Sara and Schneider, Lon S and
Pawluczyk, Sonia and Beccera, Mauricio and Teodoro, Liberty
and Spann, Bryan M and Brewer, James and Vanderswag, Helen
and Fleisher, Adam and Heidebrink, Judith L and Lord, Joanne
L and Petersen, Ronald and Mason, Sara S and Albers, Colleen
S and Knopman, David and Johnson, Kris and Doody, Rachelle S
and Villanueva-Meyer, Javier and Chowdhury, Munir and
Rountree, Susan and Dang, Mimi and Stern, Yaakov and Honig,
Lawrence S and Bell, Karen L and Ances, Beau and Morris,
John C and Carroll, Maria and Creech, Mary L and Franklin,
Erin and Mintun, Mark A and Schneider, Stacy and Oliver,
Angela and Marson, Daniel and Griffith, Randall and Clark,
David and Geldmacher, David and Brockington, John and
Roberson, Erik and Love, Marissa Natelson and Grossman,
Hillel and Mitsis, Effie and Shah, Raj C and
deToledo-Morrell, Leyla and Duara, Ranjan and Varon, Daniel
and Greig, Maria T and Roberts, Peggy and Albert, Marilyn
and Onyike, Chiadi and D' Agostino, Daniel and Kielb,
Stephanie and Galvin, James E and Cerbone, Brittany and
Michel, Christina A and Pogorelec, Dana M and Rusinek, Henry
and de Leon, Mony J and Glodzik, Lidia and De Santi, Susan
and Doraiswamy, P Murali and Petrella, Jeffrey R and
Borges-Neto, Salvador and Wong, Terence Z and Coleman,
Edward and Arnold, Steven E and Karlawish, Jason H and Wolk,
David and Clark, Christopher M and Smith, Charles D and
Jicha, Greg and Hardy, Peter and Sinha, Partha and Oates,
Elizabeth and Conrad, Gary and Lopez, Oscar L and Oakley,
MaryAnn and Simpson, Donna M and Porsteinsson, Anton P and
Goldstein, Bonnie S and Martin, Kim and Makino, Kelly M and
Ismail, M Saleem and Brand, Connie and Mulnard, Ruth A and
Thai, Gaby and Mc-Adams-Ortiz, Catherine and Womack, Kyle
and Mathews, Dana and Quiceno, Mary and Levey, Allan I and
Lah, James J and Cellar, Janet S and Burns, Jeffrey M and
Swerdlow, Russell H and Brooks, William M and Apostolova,
Liana and Tingus, Kathleen and Woo, Ellen and Silverman,
Daniel H S and Lu, Po H and Bartzokis, George and
Graff-Radford, Neill R and Parfitt, Francine and Kendall,
Tracy and Johnson, Heather and Farlow, Martin R and Hake,
Ann Marie and Matthews, Brandy R and Brosch, Jared R and
Herring, Scott and Hunt, Cynthia and van Dyck, Christopher H
and Carson, Richard E and MacAvoy, Martha G and Varma,
Pradeep and Chertkow, Howard and Bergman, Howard and Hosein,
Chris and Black, Sandra and Stefanovic, Bojana and Caldwell,
Curtis and Hsiung, Ging-Yuek Robin and Feldman, Howard and
Mudge, Benita and Assaly, Michele and Finger, Elizabeth and
Pasternack, Stephen and Rachisky, Irina and Trost, Dick and
Kertesz, Andrew and Bernick, Charles and Munic, Donna and
Mesulam, Marek-Marsel and Lipowski, Kristine and Weintraub,
MaSandra and Bonakdarpour, Borna and Kerwin, Diana and Wu,
Chuang-Kuo and Johnson, Nancy and Sadowsky, Carl and
Villena, Teresa and Turner, Raymond Scott and Johnson,
Kathleen and Reynolds, Brigid and Sperling, Reisa A and
Johnson, Keith A and Marshall, Gad and Yesavage, Jerome and
Taylor, Joy L and Lane, Barton and Rosen, Allyson and
Tinklenberg, Jared and Sabbagh, Marwan N and Belden,
Christine M and Jacobson, Sandra A and Sirrel, Sherye A and
Kowall, Neil and Killiany, Ronald and Budson, Andrew E and
Norbash, Alexander and Johnson, Patricia Lynn and Obisesan,
Thomas O and Wolday, Saba and Allard, Joanne and Lerner,
Alan and Ogrocki, Paula and Tatsuoka, Curtis and Fatica,
Parianne and Fletcher, Evan and Maillard, Pauline and
Olichney, John and DeCarli, Charles and Carmichael, Owen and
Kittur, Smita and Borrie, Michael and Lee, T-Y and Bartha,
Rob and Asthana, Sanjay and Carlsson, Cynthia M and Potkin,
Steven G and Preda, Adrian and Nguyen, Dana and Tariot,
Pierre and Burke, Anna and Trncic, Nadira and Fleisher, Adam
and Reeder, Stephanie and Bates, Vernice and Capote, Horacio
and Rainka, Michelle and Scharre, Douglas W and Kataki,
Maria and Adeli, Anahita and Zimmerman, Earl A and Celmins,
Dzintra and Brown, Alice D and Pearlson, Godfrey D and
Blank, Karen and Anderson, Karen and Flashman, Laura A and
Seltzer, Marc and Hynes, Mary L and Santulli, Robert B and
Sink, Kaycee M and Gordineer, Leslie and Williamson, Jeff D
and Garg, Pradeep and Watkins, Franklin and Ott, Brian R and
Querfurth, Henry and Tremont, Geoffrey and Salloway, Stephen
and Malloy, Paul and Correia, Stephen and Rosen, Howard J
and Miller, Bruce L and Perry, David and Mintzer, Jacobo and
Spicer, Kenneth and Bachman, David and Finger, Elizabether
and Pasternak, Stephen and Rachinsky, Irina and Rogers, John
and Kertesz, Andrew and Drost, Dick and Pomara, Nunzio and
Hernando, Raymundo and Sarrael, Antero and Schultz, Susan K
and Ponto, Laura L Boles and Shim, Hyungsub and Smith, Karen
Ekstam and Relkin, Norman and Chaing, Gloria and Lin,
Michael and Ravdin, Lisa and Smith, Amanda and Raj, Balebail
Ashok and Fargher, Kristin and Weiner, Michael W and Aisen,
Paul and Weiner, Michael and Aisen, Paul and Petersen,
Ronald and Green, Robert C and Harvey, Danielle and Jack,
Clifford R and Jagust, William and Morris, John C and
Saykin, Andrew J and Shaw, Leslie M and Trojanowki, John Q
and Neylan, Thomas and Grafman, Jordan and Green, Robert C
and Montine, Tom and Weiner, Michael and Petersen, Ronald
and Aisen, Paul and Thomas, Ronald G and Donohue, Michael
and Gessert, Devon and Sather, Tamie and Davis, Melissa and
Morrison, Rosemary and Jiminez, Gus and Neylan, Thomas and
Hayes, Jacqueline and Finley, Shannon and Harvey, Danielle
and Donohue, Michael and Jack, Clifford R and Bernstein,
Matthew and Borowski, Bret and Gunter, Jeff and Senjem, Matt
and Kantarci, Kejal and Jagust, William and Koeppe, Robert A
and Foster, Norm and Reiman, Eric M and Chen, Kewei and
Landau, Susan and Morris, John C and Cairns, Nigel J and
Householder, Erin and Shaw, Leslie M and Trojanowki, John Q
and Lee, Virginia and Korecka, Magdalena and Figurski,
Michal and Toga, Arthur W and Crawford, Karen and Neu, Scott
and Saykin, Andrew J and Foroud, Tatiana M and Potkin,
Steven and Shen, Li and Faber, Kelley and Kim, Sungeun and
Weiner, Michael W and Schneider, Lon S and Pawluczyk, Sonia
and Beccera, Mauricio and Brewer, James and Vanderswag,
Helen and Stern, Yaakov and Honig, Lawrence S and Bell,
Karen L and Fleischman, Debra and Arfanakis, Konstantinos
and Shah, Raj C and Duara, Ranjan and Varon, Daniel and
Greig, Maria T and Doraiswamy, P Murali and Petrella,
Jeffrey R and James, Olga and Porsteinsson, Anton P and
Goldstein, Bonnie and Martin, Kimberly S and Mulnard, Ruth A
and Thai, Gaby and McAdams-Ortiz, Catherine and Mintzer,
Jacobo and Massoglia, Dino and Brawman-Mintzer, Olga and
Sadowsky, Carl and Martinez, Walter and Villena, Teresa and
Jagust, William and Landau, Susan and Rosen, Howard and
Perry, David and Turner, Raymond Scott and Behan, Kelly and
Reynolds, Brigid and Sperling, Reisa A and Johnson, Keith A
and Marshall, Gad and Sabbagh, Marwan N and Jacobson, Sandra
A and Sirrel, Sherye A and Obisesan, Thomas O and Wolday,
Saba and Allard, Joanne and Johnson, Sterling C and
Fruehling, J Jay and Harding, Sandra and Peskind, Elaine R
and Petrie, Eric C and Li, Gail and Yesavage, Jerome A and
Taylor, Joy L and Furst, Ansgar J and Chao, Steven and
Relkin, Norman and Chaing, Gloria and Ravdin, Lisa},
title = {{A}lzheimer's disease cerebrospinal fluid biomarker in
cognitively normal subjects.},
journal = {Brain},
volume = {138},
number = {9},
issn = {0006-8950},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DZNE-2020-04443},
pages = {2701-2715},
year = {2015},
abstract = {In a large multicentre sample of cognitively normal
subjects, as a function of age, gender and APOE genotype, we
studied the frequency of abnormal cerebrospinal fluid levels
of Alzheimer's disease biomarkers including: total tau,
phosphorylated tau and amyloid-β1-42. Fifteen cohorts from
12 different centres with either enzyme-linked immunosorbent
assays or Luminex® measurements were selected for this
study. Each centre sent nine new cerebrospinal fluid
aliquots that were used to measure total tau, phosphorylated
tau and amyloid-β1-42 in the Gothenburg laboratory. Seven
centres showed a high correlation with the new Gothenburg
measurements; therefore, 10 cohorts from these centres are
included in the analyses here (1233 healthy control
subjects, 40-84 years old). Amyloid-β amyloid status
(negative or positive) and neurodegeneration status
(negative or positive) was established based on the
pathological cerebrospinal fluid Alzheimer's disease cut-off
values for cerebrospinal fluid amyloid-β1-42 and total tau,
respectively. While gender did not affect these biomarker
values, APOE genotype modified the age-associated changes in
cerebrospinal fluid biomarkers such that APOE ε4 carriers
showed stronger age-related changes in cerebrospinal fluid
phosphorylated tau, total tau and amyloid-β1-42 values and
APOE ε2 carriers showed the opposite effect. At 40 years of
age, $76\%$ of the subjects were classified as amyloid
negative, neurodegeneration negative and their frequency
decreased to $32\%$ at 85 years. The amyloid-positive
neurodegeneration-negative group remained stable. The
amyloid-negative neurodegeneration-positive group frequency
increased slowly from $1\%$ at 44 years to $16\%$ at 85
years, but its frequency was not affected by APOE genotype.
The amyloid-positive neurodegeneration-positive frequency
increased from $1\%$ at 53 years to $28\%$ at 85 years.
Abnormally low cerebrospinal fluid amyloid-β1-42 levels
were already frequent in midlife and APOE genotype strongly
affects the levels of cerebrospinal fluid amyloid-β1-42,
phosphorylated tau and total tau across the lifespan without
influencing the frequency of subjects with suspected
non-amyloid pathology.},
keywords = {Adult / Age Factors / Aged / Aged, 80 and over / Alzheimer
Disease: cerebrospinal fluid / Alzheimer Disease: genetics /
Alzheimer Disease: physiopathology / Amyloid beta-Peptides:
cerebrospinal fluid / Analysis of Variance / Apolipoproteins
E: genetics / Cognition: physiology / Cohort Studies /
Female / Humans / Male / Middle Aged / Neurodegenerative
Diseases: etiology / Neuropsychological Tests / Peptide
Fragments: cerebrospinal fluid / Severity of Illness Index /
tau Proteins: cerebrospinal fluid / Amyloid beta-Peptides
(NLM Chemicals) / Apolipoproteins E (NLM Chemicals) /
Peptide Fragments (NLM Chemicals) / amyloid beta-protein
(1-42) (NLM Chemicals) / tau Proteins (NLM Chemicals)},
cin = {Clinical Dementia Research Rostock /Greifswald},
ddc = {610},
cid = {I:(DE-2719)1510100},
pnm = {344 - Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26220940},
pmc = {pmc:PMC4643624},
doi = {10.1093/brain/awv199},
url = {https://pub.dzne.de/record/138121},
}
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