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Multimodal characterization of older APOE2 carriers reveals selective reduction of amyloid load

Multimodal characterization of older APOE2 carriers reveals selective reduction of amyloid load

Authors :
Grothe, Michel J
Villeneuve, Sylvia
Petersen, Ronald
Leyla deToledo-Morrell, PhD
Shah, Raj C
Duara, Ranjan
Varon, Daniel
Roberts Cna, Peggy
Albert, Marilyn
Onyike, Chiadi
Kielb, Stephanie
Rusinek, Henry
de Leon, Mony J
Jack, Clifford R
Glodzik, Lidia
De Santi, Susan
Doraiswamy, P Murali
Petrella, Jeffrey R
Coleman, R Edward
Arnold, Steven E
Karlawish, Jason H
Wolk, David
Smith, Charles D
Jicha, Greg
Jagust, William
Hardy, Peter
Lopez, Oscar L
Oakley, MaryAnn
Simpson, Donna M
Porsteinsson, Anton P
Goldstein, Bonnie S
Martin, Kim
Makino, Kelly M
Ismail, M Saleem
Brand, Connie
Trojanowki, John Q
Mulnard, Ruth A
Thai, Gaby
Mc-Adams-Ortiz, Catherine
Womack, Kyle
Mathews, Dana
Quiceno, Mary
Diaz-Arrastia, Ramon
King, Richard
Weiner, Myron
Martin-Cook, Kristen
Toga, Arthur W
DeVous, Michael
Levey, Allan I
Lah, James J
Cellar, Janet S
Burns, Jeffrey M
Anderson, Heather S
Swerdlow, Russell H
Apostolova, Liana
Lu, Po H
Bartzokis, George
Beckett, Laurel
Silverman, Daniel H S
Graff-Radford Mbbch, Neill R
Parfitt, Francine
Johnson, Heather
Farlow, Martin R
Hake, Ann Marie
Matthews, Brandy R
Herring, Scott
van Dyck, Christopher H
Carson, Richard E
Green, Robert C
MacAvoy, Martha G
Chertkow, Howard
Bergman, Howard
Hosein, Chris
Black, Sandra
Stefanovic, Bojana
Caldwell, Curtis
Robin Hsiung, Ging-Yuek
Feldman, Howard
Mudge, Benita
Saykin, Andrew J
Assaly, Michele
Kertesz, Andrew
Rogers, John
Trost, Dick
Bernick, Charles
Munic, Donna
Kerwin, Diana
Mesulam, Marek-Marsel
Lipowski, Kristina
Wu, Chuang-Kuo
Morris, John
Johnson, Nancy
Sadowsky, Carl
Martinez, Walter
Villena, Teresa
Turner, Raymond Scott
Johnson, Kathleen
Reynolds, Brigid
Sperling, Reisa A
Johnson, Keith A
Marshall, Gad
Liu, Enchi
Frey, Meghan
Yesavage, Jerome
Taylor, Joy L
Lane, Barton
Rosen, Allyson
Tinklenberg, Jared
Sabbagh, Marwan
Belden, Christine
Jacobson, Sandra
Kowall, Neil
Dyrba, Martin
Killiany, Ronald
Budson, Andrew E
Norbash, Alexander
Johnson, Patricia Lynn
Obisesan, Thomas O
Wolday, Saba
Bwayo, Salome K
Lerner, Alan
Hudson, Leon
Ogrocki, Paula
Montine, Tom
Fletcher, Evan
Carmichael, Owen
Olichney, John
DeCarli, Charles
Kittur, Smita
Borrie, Michael
Lee, T-Y
Bartha, Dr Rob
Johnson, Sterling
Asthana, Sanjay
Carlsson, Cynthia M
Potkin, Steven G
Preda, Adrian
Nguyen, Dana
Tariot, Pierre
Fleisher, Adam
Reeder, Stephanie
Bates, Vernice
Capote, Horacio
Rainka, Michelle
Aisen, Paul
Scharre, Douglas W
Kataki, Maria
Zimmerman, Earl A
Celmins, Dzintra
Brown, Alice D
Pearlson, Godfrey D
Blank, Karen
Anderson, Karen
Santulli, Robert B
Gamst, Anthony
Schwartz, Eben S
Sink, Kaycee M
Williamson, Jeff D
Garg, Pradeep
Watkins, Franklin
Ott, Brian R
Querfurth, Henry
Tremont, Geoffrey
Salloway, Stephen
Malloy, Paul
Thomas, Ronald G
Correia, Stephen
Rosen, Howard J
Miller, Bruce L
Mintzer, Jacobo
Longmire, Crystal Flynn
Spicer, Kenneth
Finger, Elizabether
Rachinsky, Irina
Donohue, Michael
Drost, Dick
Pomara, Nunzio
Hernando, Raymundo
Sarrael, Antero
Schultz, Susan K
Boles Ponto, Laura L
Shim, Hyungsub
Smith, Karen Elizabeth
Relkin, Norman
Chaing, Gloria
Walter, Sarah
Raudin, Lisa
Smith, Amanda
Fargher, Kristin
Raj, Balebail Ashok
Gessert, Devon
Sather, Tamie
Bartrés-Faz, David
Harvey, Danielle
Kornak, John
Dale, Anders
Bernstein, Matthew
Felmlee, Joel
Fox, Nick
Wirth, Miranka
Thompson, Paul
Schuff, Norbert
Alexander, Gene
Bandy, Dan
Koeppe, Robert A
Foster, Norm
Reiman, Eric M
Chen, Kewei
Initiative, Alzheimer's Disease Neuroimaging
Mathis, Chet
Cairns, Nigel J
Taylor-Reinwald, Lisa
Trojanowki, J. Q.
Shaw, Les
Lee, Virginia M Y
Korecka, Magdalena
Crawford, Karen
Weiner, Michael
Neu, Scott
Foroud, Tatiana M
Potkin, Steven
Shen, Li
Kachaturian, Zaven
Frank, Richard
Snyder, Peter J
Molchan, Susan
Kaye, Jeffrey
Quinn, Joseph
Lind, Betty
Dolen, Sara
Schneider, Lon S
Pawluczyk, Sonia
Spann, Bryan M
Brewer, James
Vanderswag, Helen
Heidebrink, Judith L
Lord, Joanne L
Johnson, Kris
Doody, Rachelle S
Villanueva-Meyer, Javier
Chowdhury, Munir
Stern, Yaakov
Honig, Lawrence S
Bell, Karen L
Morris, John C
Ances, Beau
Carroll, Maria
Leon, Sue
Mintun, Mark A
Schneider, Stacy
Marson, Daniel
Griffith, Randall
Clark, David
Grossman, Hillel
Mitsis, Effie
Romirowsky, Aliza
Source :
Neurology 88(6), 569-576 (2017). doi:10.1212/WNL.0000000000003585
Publication Year :
2016

Abstract

Objective:To comprehensively assess neurobiological effects of the protective APOE2 allele in the aged brain using a cross-sectional multimodal neuroimaging approach.Methods: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.Results: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.Conclusions: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.

Details

ISSN :
1526632X
Volume :
88
Issue :
6
Database :
OpenAIRE
Journal :
Neurology
Accession number :
edsair.doi.dedup.....b2e14f62236fbe531ce6e56e372f4183
Full Text :
https://doi.org/10.1212/WNL.0000000000003585