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Neurology. 2017 Feb 7;88(6):569-576. doi: 10.1212/WNL.0000000000003585. Epub 2017 Jan 6.

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

Collaborators (268)

Weiner M, Aisen P, Weiner M, Aisen P, Petersen R, Jack CR Jr, Jagust W, Trojanowki JQ, Toga AW, Beckett L, Green RC, Saykin AJ, Morris J, Liu E, Green RC, Montine T, Petersen R, Aisen P, Gamst A, Thomas RG, Donohue M, Walter S, Gessert D, Sather T, Beckett L, Harvey D, Gamst A, Donohue M, Kornak J, Jack CR Jr, Dale A, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, DeCarli C, Jagust W, Bandy D, Koeppe RA, Foster N, Reiman EM, Chen K, Mathis C, Morris J, Cairns NJ, Taylor-Reinwald L, Trojanowki JQ, Shaw L, Lee VM, Korecka M, Toga AW, Crawford K, Neu S, Saykin AJ, Foroud TM, Potkin S, Shen L, Kachaturian Z, Frank R, Snyder PJ, Molchan S, Kaye J, Quinn J, Lind B, Dolen S, Schneider LS, Pawluczyk S, Spann BM, Brewer J, Vanderswag H, Heidebrink JL, Lord JL, Petersen R, Johnson K, Doody RS, Villanueva-Meyer J, Chowdhury M, Stern Y, Honig LS, Bell KL, Morris JC, Ances B, Carroll M, Leon S, Mintun MA, Schneider S, Marson D, Griffith R, Clark D, Grossman H, Mitsis E, Romirowsky A, Leyla deToledo-Morrell P, Shah RC, Duara R, Varon D, Roberts Cna P, Albert M, Onyike C, Kielb S, Rusinek H, de Leon MJ, Glodzik L, De Santi S, Doraiswamy PM, Petrella JR, Coleman RE, Arnold SE, Karlawish JH, Wolk D, Smith CD, Jicha G, Hardy P, Lopez OL, Oakley M, Simpson DM, Porsteinsson AP, Goldstein BS, Martin K, Makino KM, Ismail MS, Brand C, Mulnard RA, Thai G, Mc-Adams-Ortiz C, Womack K, Mathews D, Quiceno M, Diaz-Arrastia R, King R, Weiner M, Martin-Cook K, DeVous M, Levey AI, Lah JJ, Cellar JS, Burns JM, Anderson HS, Swerdlow RH, Apostolova L, Lu PH, Bartzokis G, Silverman DH, Graff-Radford Mbbch NR, Parfitt F, Johnson H, Farlow MR, Hake AM, Matthews BR, Herring S, van Dyck CH, Carson RE, MacAvoy MG, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Robin Hsiung GY, Feldman H, Mudge B, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Kerwin D, Mesulam MM, Lipowski K, Wu CK, Johnson N, Sadowsky C, Martinez W, Villena T, Turner RS, Johnson K, Reynolds B, Sperling RA, Johnson KA, Marshall G, Frey M, Yesavage J, Taylor JL, Lane B, Rosen A, Tinklenberg J, Sabbagh M, Belden C, Jacobson S, Kowall N, Killiany R, Budson AE, Norbash A, Johnson PL, Obisesan TO, Wolday S, Bwayo SK, Lerner A, Hudson L, Ogrocki P, Fletcher E, Carmichael O, Olichney J, DeCarli C, Kittur S, Borrie M, Lee TY, Bartha DR, Johnson S, Asthana S, Carlsson CM, Potkin SG, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Scharre DW, Kataki M, Zimmerman EA, Celmins D, Brown AD, Pearlson GD, Blank K, Anderson K, Saykin AJ, Santulli RB, Schwartz ES, Sink KM, Williamson JD, Garg P, Watkins F, Ott BR, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen HJ, Miller BL, Mintzer J, Longmire CF, Spicer K, Finger E, Rachinsky I, Rogers J, Kertesz A, Drost D, Pomara N, Hernando R, Sarrael A, Schultz SK, Boles Ponto LL, Shim H, Smith KE, Relkin N, Chaing G, Raudin L, Smith A, Fargher K, Raj BA.

Author information

1
From the German Center for Neurodegenerative Diseases (M.J.G., M.D.), Rostock, Germany; Douglas Mental Health University Institute (S.V.), Research Centre, Verdun; Department of Psychiatry (S.V.), McGill University, Montreal, Quebec, Canada; Department of Medicine (D.B.-F.), Faculty of Medicine and Health Sciences, University of Barcelona, Spain; and NeuroCure Clinical Research Center (M.W.) and Department of Neurology, Charité-Universitätsmedizin Berlin, Germany. michel.grothe@dzne.de.
2
From the German Center for Neurodegenerative Diseases (M.J.G., M.D.), Rostock, Germany; Douglas Mental Health University Institute (S.V.), Research Centre, Verdun; Department of Psychiatry (S.V.), McGill University, Montreal, Quebec, Canada; Department of Medicine (D.B.-F.), Faculty of Medicine and Health Sciences, University of Barcelona, Spain; and NeuroCure Clinical Research Center (M.W.) and Department of Neurology, Charité-Universitätsmedizin Berlin, Germany.

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.

PMID:
28062720
PMCID:
PMC5304459
DOI:
10.1212/WNL.0000000000003585
[Indexed for MEDLINE]
Free PMC Article

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