Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
23028511
TITLE
Plasma based markers of [11C] PiB-PET brain amyloid burden.
ABSTRACT
Changes in brain amyloid burden have been shown to relate to Alzheimer's disease pathology, and are believed to precede the development of cognitive decline. There is thus a need for inexpensive and non-invasive screening methods that are able to accurately estimate brain amyloid burden as a marker of Alzheimer's disease. One potential method would involve using demographic information and measurements on plasma samples to establish biomarkers of brain amyloid burden; in this study data from the Alzheimer's Disease Neuroimaging Initiative was used to explore this possibility. Sixteen of the analytes on the Rules Based Medicine Human Discovery Multi-Analyte Profile 1.0 panel were found to associate with [(11)C]-PiB PET measurements. Some of these markers of brain amyloid burden were also found to associate with other AD related phenotypes. Thirteen of these markers of brain amyloid burden--c-peptide, fibrinogen, alpha-1-antitrypsin, pancreatic polypeptide, complement C3, vitronectin, cortisol, AXL receptor kinase, interleukin-3, interleukin-13, matrix metalloproteinase-9 total, apolipoprotein E and immunoglobulin E--were used along with co-variates in multiple linear regression, and were shown by cross-validation to explain >30% of the variance of brain amyloid burden. When a threshold was used to classify subjects as PiB positive, the regression model was found to predict actual PiB positive individuals with a sensitivity of 0.918 and a specificity of 0.545. The number of APOE [Symbol: see text] 4 alleles and plasma apolipoprotein E level were found to contribute most to this model, and the relationship between these variables and brain amyloid burden was explored.
DATE PUBLISHED
2012
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/04/13
accepted 2012/07/31
epublish 2012/09/24
entrez 2012/10/03 06:00
pubmed 2012/10/03 06:00
medline 2013/03/21 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Kiddle SJ Kiddle Steven John SJ National Institute of Health Research Biomedical Research Centre for Mental Health, South London and Maudsley National Health Service Foundation Trust, London, United Kingdom. steven.kiddle@kcl.ac.uk
Thambisetty M Thambisetty Madhav M
Simmons A Simmons Andrew A
Riddoch-Contreras J Riddoch-Contreras Joanna J
Hye A Hye Abdul A
Westman E Westman Eric E
Pike I Pike Ian I
Ward M Ward Malcolm M
Johnston C Johnston Caroline C
Lupton MK Lupton Michelle Katharine MK
Lunnon K Lunnon Katie K
Soininen H Soininen Hilkka H
Kloszewska I Kloszewska Iwona I
Tsolaki M Tsolaki Magda M
Vellas B Vellas Bruno B
Mecocci P Mecocci Patrizia P
Lovestone S Lovestone Simon S
Newhouse S Newhouse Stephen S
Dobson R Dobson Richard R
Alzheimers Disease Neuroimaging Initiative
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Weiner Michael M
Aisen Paul P
Weiner Michael M
Aisen Paul P
Petersen Ronald R
Jack Clifford R CR
Jagust William W
Trojanowki John Q JQ
Toga Arthur W AW
Beckett Laurel L
Green Robert C RC
Saykin Andrew J AJ
Morris John J
Liu Enchi E
Green Robert C RC
Montine Tom T
Petersen Ronald R
Aisen Paul P
Gamst Anthony A
Thomas Ronald G RG
Donohue Michael M
Walter Sarah S
Gessert Devon D
Sather Tamie T
Beckett Laurel L
Harvey Danielle D
Gamst Anthony A
Donohue Michael M
Kornak John J
Jack Clifford R CR
Dale Anders A
Bernstein Matthew M
Felmlee Joel J
Fox Nick N
Thompson Paul P
Schuff Norbert N
Alexander Gene G
DeCarli Charles C
Jagust William W
Bandy Dan D
Koeppe Robert A RA
Foster Norm N
Reiman Eric M EM
Chen Kewei K
Mathis Chet C
Morris John J
Cairns Nigel J NJ
Taylor-Reinwald Lisa L
Trojanowki J Q JQ
Shaw Les L
Lee Virginia M Y VM
Korecka Magdalena M
Toga Arthur W AW
Crawford Karen K
Neu Scott S
Saykin Andrew J AJ
Foroud Tatiana M TM
Potkin Steven S
Shen Li L
Kachaturian Zaven Z
Frank Richard R
Snyder Peter J PJ
Molchan Susan S
Kaye Jeffrey J
Quinn Joseph J
Lind Betty B
Dolen Sara S
Schneider Lon S LS
Pawluczyk Sonia S
Spann Bryan M BM
Brewer James J
Vanderswag Helen H
Heidebrink Judith L JL
Lord Joanne L JL
Petersen Ronald R
Johnson Kris K
Doody Rachelle S RS
Villanueva-Meyer Javier J
Chowdhury Munir M
Stern Yaakov Y
Honig Lawrence S LS
Bell Karen L KL
Morris John C JC
Ances Beau B
Carroll Maria M
Leon Sue S
Mintun Mark A MA
Schneider Stacy S
Marson Daniel D
Griffith Randall R
Clark David D
Grossman Hillel H
Mitsis Effie E
Romirowsky Aliza A
deToledo-Morrell Leyla L
Shah Raj C RC
Duara Ranjan R
Varon Daniel D
Roberts Peggy P
Albert Marilyn M
Onyike Chiadi C
Kielb Stephanie S
Rusinek Henry H
de Leon Mony J MJ
Glodzik Lidia L
De Santi Susan S
Doraiswamy P Murali P
Petrella Jeffrey R JR
Coleman R Edward R
Arnold Steven E SE
Karlawish Jason H JH
Wolk David D
Smith Charles D CD
Jicha Greg G
Hardy Peter P
Lopez Oscar L OL
Oakley MaryAnn M
Simpson Donna M DM
Porsteinsson Anton P AP
Goldstein Bonnie S BS
Martin Kim K
Makino Kelly M KM
Ismail M Saleem M
Brand Connie C
Mulnard Ruth A RA
Thai Gaby G
Mc-Adams-Ortiz Catherine C
Womack Kyle K
Mathews Dana D
Quiceno Mary M
Diaz-Arrastia Ramon R
King Richard R
Weiner Myron M
Martin-Cook Kristen K
DeVous Michael M
Levey Allan I AI
Lah James J JJ
Cellar Janet S JS
Burns Jeffrey M JM
Anderson Heather S HS
Swerdlow Russell H RH
Apostolova Liana L
Lu Po H PH
Bartzokis George G
Silverman Daniel H S DH
Graff-Radford Neill R NR
Parfitt Francine F
Johnson Heather H
Farlow Martin R MR
Hake Ann Marie AM
Matthews Brandy R BR
Herring Scott S
van Dyck Christopher H CH
Carson Richard E RE
MacAvoy Martha G MG
Chertkow Howard H
Bergman Howard H
Hosein Chris C
Black Sandra S
Stefanovic Bojana B
Caldwell Curtis C
Hsiung Ging-Yuek Robin GY
Feldman Howard H
Mudge Benita B
Assaly Michele M
Kertesz Andrew A
Rogers John J
Trost Dick D
Bernick Charles C
Munic Donna D
Kerwin Diana D
Mesulam Marek-Marsel MM
Lipowski Kristina K
Wu Chuang-Kuo CK
Johnson Nancy N
Sadowsky Carl C
Martinez Walter W
Villena Teresa T
Turner Raymond Scott RS
Johnson Kathleen K
Reynolds Brigid B
Sperling Reisa A RA
Johnson Keith A KA
Marshall Gad G
Frey Meghan M
Yesavage Jerome J
Taylor Joy L JL
Lane Barton B
Rosen Allyson A
Tinklenberg Jared J
Sabbagh Marwan M
Belden Christine C
Jacobson Sandra S
Kowall Neil N
Killiany Ronald R
Budson Andrew E AE
Norbash Alexander A
Johnson Patricia Lynn PL
Obisesan Thomas O TO
Wolday Saba S
Bwayo Salome K SK
Lerner Alan A
Hudson Leon L
Ogrocki Paula P
Fletcher Evan E
Carmichael Owen O
Olichney John J
DeCarli Charles C
Kittur Smita S
Borrie Michael M
Lee T-Y TY
Bartha Rob R
Asthana Sanjay S
Carlsson Cynthia M CM
Potkin Steven G SG
Preda Adrian A
Nguyen Dana D
Tariot Pierre P
Fleisher Adam A
Reeder Stephanie S
Bates Vernice V
Capote Horacio H
Rainka Michelle M
Scharre Douglas W DW
Kataki Maria M
Zimmerman Earl A EA
Celmins Dzintra D
Brown Alice D AD
Pearlson Godfrey D GD
Blank Karen K
Anderson Karen K
Saykin Andrew J AJ
Santulli Robert B RB
Schwartz Eben S ES
Sink Kaycee M KM
Williamson Jeff D JD
Garg Pradeep P
Watkins Franklin F
Ott Brian R BR
Querfurth Henry H
Tremont Geoffrey G
Salloway Stephen S
Malloy Paul P
Correia Stephen S
Rosen Howard J HJ
Miller Bruce L BL
Mintzer Jacobo J
Flynn Longmire Crystal C
Spicer Kenneth K
Finger Elizabether E
Rachinsky Irina I
Rogers John J
Kertesz Andrew A
Drost Dick D
JOURNAL
VOLUME: 7
ISSUE: 9
TITLE: PloS one
ISOABBREVIATION: PLoS ONE
YEAR: 2012
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1932-6203
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS One
COUNTRY: United States
ISSNLINKING: 1932-6203
NLMUNIQUEID: 101285081
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
K01 AG030514 NIA NIH HHS United States
P30 AG010129 NIA NIH HHS United States
P30 AG019610 NIA NIH HHS United States
U01 AG024904 NIA NIH HHS United States
UL1 TR000117 NCATS NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Aged
Aged, 80 and over
Alzheimer Disease radionuclide imaging
Amyloid beta-Peptides metabolism
Aniline Compounds metabolism
Apolipoproteins E metabolism
Biomarkers blood
Brain radionuclide imaging
Cluster Analysis radionuclide imaging
Female radionuclide imaging
Genotype radionuclide imaging
Humans radionuclide imaging
Male radionuclide imaging
Metabolome radionuclide imaging
Metabolomics radionuclide imaging
Middle Aged radionuclide imaging
Positron-Emission Tomography radionuclide imaging
Prognosis radionuclide imaging
Reproducibility of Results radionuclide imaging
Thiazoles radionuclide imaging
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
0 Amyloid beta-Peptides
0 Aniline Compounds
0 Apolipoproteins E
0 Biomarkers
0 Thiazoles
OTHER ID's
OTHERID SOURCE
PMC3454385 NLM