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@ARTICLE{Grothe:139144,
author = {Grothe, Michel J and Villeneuve, Sylvia and Dyrba, Martin
and Bartrés-Faz, David and Wirth, Miranka and Initiative,
Alzheimer's Disease Neuroimaging and Weiner, Michael 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 Liu, Enchi and Green, Robert C and Montine, Tom and
Petersen, Ronald and Aisen, Paul and Gamst, Anthony and
Thomas, Ronald G and Donohue, Michael and Walter, Sarah and
Gessert, Devon and Sather, Tamie and Beckett, Laurel and
Harvey, Danielle and Gamst, Anthony and Donohue, Michael and
Kornak, John and Jack, Clifford R and Dale, Anders and
Bernstein, Matthew and Felmlee, Joel and Fox, Nick and
Thompson, Paul and Schuff, Norbert and Alexander, Gene and
DeCarli, Charles and Jagust, William and Bandy, Dan and
Koeppe, Robert A and Foster, Norm and Reiman, Eric M and
Chen, Kewei and Mathis, Chet and Morris, John and Cairns,
Nigel J and Taylor-Reinwald, Lisa and Trojanowki, J. Q. and
Shaw, Les and Lee, Virginia M Y and Korecka, Magdalena 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 Kachaturian, Zaven and Frank, Richard and
Snyder, Peter J and Molchan, Susan and Kaye, Jeffrey and
Quinn, Joseph and Lind, Betty and Dolen, Sara and Schneider,
Lon S and Pawluczyk, Sonia and Spann, Bryan M and Brewer,
James and Vanderswag, Helen and Heidebrink, Judith L and
Lord, Joanne L and Petersen, Ronald and Johnson, Kris and
Doody, Rachelle S and Villanueva-Meyer, Javier and
Chowdhury, Munir and Stern, Yaakov and Honig, Lawrence S and
Bell, Karen L and Morris, John C and Ances, Beau and
Carroll, Maria and Leon, Sue and Mintun, Mark A and
Schneider, Stacy and Marson, Daniel and Griffith, Randall
and Clark, David and Grossman, Hillel and Mitsis, Effie and
Romirowsky, Aliza and Leyla deToledo-Morrell, PhD and Shah,
Raj C and Duara, Ranjan and Varon, Daniel and Roberts Cna,
Peggy and Albert, Marilyn and Onyike, Chiadi and Kielb,
Stephanie and Rusinek, Henry and de Leon, Mony J and
Glodzik, Lidia and De Santi, Susan and Doraiswamy, P Murali
and Petrella, Jeffrey R and Coleman, R Edward and Arnold,
Steven E and Karlawish, Jason H and Wolk, David and Smith,
Charles D and Jicha, Greg and Hardy, Peter 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
Diaz-Arrastia, Ramon and King, Richard and Weiner, Myron and
Martin-Cook, Kristen and DeVous, Michael and Levey, Allan I
and Lah, James J and Cellar, Janet S and Burns, Jeffrey M
and Anderson, Heather S and Swerdlow, Russell H and
Apostolova, Liana and Lu, Po H and Bartzokis, George and
Silverman, Daniel H S and Graff-Radford Mbbch, Neill R and
Parfitt, Francine and Johnson, Heather and Farlow, Martin R
and Hake, Ann Marie and Matthews, Brandy R and Herring,
Scott and van Dyck, Christopher H and Carson, Richard E and
MacAvoy, Martha G and Chertkow, Howard and Bergman, Howard
and Hosein, Chris and Black, Sandra and Stefanovic, Bojana
and Caldwell, Curtis and Robin Hsiung, Ging-Yuek and
Feldman, Howard and Mudge, Benita and Assaly, Michele and
Kertesz, Andrew and Rogers, John and Trost, Dick and
Bernick, Charles and Munic, Donna and Kerwin, Diana and
Mesulam, Marek-Marsel and Lipowski, Kristina and Wu,
Chuang-Kuo and Johnson, Nancy and Sadowsky, Carl and
Martinez, Walter 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
Frey, Meghan and Yesavage, Jerome and Taylor, Joy L and
Lane, Barton and Rosen, Allyson and Tinklenberg, Jared and
Sabbagh, Marwan and Belden, Christine and Jacobson, Sandra
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 Bwayo, Salome K and
Lerner, Alan and Hudson, Leon and Ogrocki, Paula and
Fletcher, Evan and Carmichael, Owen and Olichney, John and
DeCarli, Charles and Kittur, Smita and Borrie, Michael and
Lee, T-Y and Bartha, Dr Rob and Johnson, Sterling and
Asthana, Sanjay and Carlsson, Cynthia M and Potkin, Steven G
and Preda, Adrian and Nguyen, Dana and Tariot, Pierre and
Fleisher, Adam and Reeder, Stephanie and Bates, Vernice and
Capote, Horacio and Rainka, Michelle and Scharre, Douglas W
and Kataki, Maria and Zimmerman, Earl A and Celmins, Dzintra
and Brown, Alice D and Pearlson, Godfrey D and Blank, Karen
and Anderson, Karen and Saykin, Andrew J and Santulli,
Robert B and Schwartz, Eben S and Sink, Kaycee M 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 Mintzer, Jacobo
and Longmire, Crystal Flynn and Spicer, Kenneth and Finger,
Elizabether 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 Boles Ponto, Laura L and Shim, Hyungsub and Smith, Karen
Elizabeth and Relkin, Norman and Chaing, Gloria and Raudin,
Lisa and Smith, Amanda and Fargher, Kristin and Raj,
Balebail Ashok},
title = {{M}ultimodal characterization of older {APOE}2 carriers
reveals selective reduction of amyloid load.},
journal = {Neurology},
volume = {88},
number = {6},
issn = {0028-3878},
address = {[S.l.]},
publisher = {Ovid},
reportid = {DZNE-2020-05466},
pages = {569-576},
year = {2017},
abstract = {To comprehensively assess neurobiological effects of the
protective APOE2 allele in the aged brain using a
cross-sectional multimodal neuroimaging approach.Multimodal
neuroimaging data were obtained from a total of 572 older
individuals without dementia (cognitively normal and mild
cognitive impairment) enrolled in the Alzheimer's Disease
Neuroimaging Initiative and included assessments of regional
amyloid load with AV45-PET, glucose metabolism with
fluorodeoxyglucose-PET, and gray matter volume with
structural MRI. Imaging indexes of APOE2 carriers were
contrasted to risk-neutral APOE3 homozygotes, and analyses
were controlled for age, sex, education, and clinical
diagnosis. Additional models examined genotype-specific
effects of age on the imaging markers.In
region-of-interest-based analyses, APOE2 carriers had
significantly less precuneal amyloid pathology and did not
show the typical age-related increase in amyloid load,
although the age × genotype interaction was only
trend-level significant. In contrast, parietal metabolism
and hippocampal volume did not differ between APOE2 and
APOE3 genotypes, and both groups showed comparable negative
effects of age on these markers. The amyloid specificity of
APOE2-related brain changes was corroborated in 2
complementary analyses: spatially unbiased voxel-wise
analyses showing widespread reductions in amyloid deposition
but no differences in gray matter volume or metabolism and
an analysis of CSF-based biomarkers showing a significant
effect on amyloid but not on tau pathology.Regarding the
range of Alzheimer disease biomarkers considered in the
present study, the APOE2 allele appears to have a relatively
selective effect on reduced accumulation of amyloid
pathology in the aged brain.},
keywords = {Aged / Aging: genetics / Aging: metabolism / Aging:
pathology / Amyloid: metabolism / Apolipoprotein E2:
genetics / Apolipoprotein E3: genetics / Biomarkers:
cerebrospinal fluid / Brain: diagnostic imaging / Brain:
metabolism / Cognitive Dysfunction: diagnostic imaging /
Cognitive Dysfunction: metabolism / Female /
Fluorodeoxyglucose F18 / Glucose: metabolism / Gray Matter:
diagnostic imaging / Gray Matter: metabolism / Heterozygote
/ Humans / Magnetic Resonance Imaging / Male / Multimodal
Imaging / Neuroimaging / Organ Size / Positron-Emission
Tomography / Radiopharmaceuticals / Amyloid (NLM Chemicals)
/ Apolipoprotein E2 (NLM Chemicals) / Apolipoprotein E3 (NLM
Chemicals) / Biomarkers (NLM Chemicals) /
Radiopharmaceuticals (NLM Chemicals) / Fluorodeoxyglucose
F18 (NLM Chemicals) / Glucose (NLM Chemicals)},
cin = {Clinical Dementia Research Rostock /Greifswald ; AG Teipel},
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:28062720},
pmc = {pmc:PMC5304459},
doi = {10.1212/WNL.0000000000003585},
url = {https://pub.dzne.de/record/139144},
}
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