Relative effect of APOE ε4 on neuroimaging biomarker changes across the lifespan.
OBJECTIVE
To provide a comprehensive understanding of APOE ε4 effects across the lifespan on the 3 main neuroimaging biomarkers.


METHODS
Two hundred seven community-dwelling, cognitively normal APOE ε4 carriers and noncarriers aged 20-87 years were involved in this study. They underwent structural MRI, fluorodeoxyglucose-PET, and florbetapir-PET scans. The effects of APOE, age, and APOE × age interaction were assessed voxel-wise for each modality.


RESULTS
There was no significant effect of APOE or APOE × age interaction on gray matter volume and glucose metabolism, although decreases with age tended to be stronger in noncarriers than in carriers. In contrast, β-amyloid (Aβ) deposition was significantly higher in carriers compared with noncarriers in a largely distributed network, and there was a significant APOE × age interaction such that Aβ deposition increased nonlinearly with age in APOE ε4 carriers only.


CONCLUSIONS
Our findings highlight a differential effect of APOE ε4 on amyloid vs neurodegeneration biomarkers. APOE ε4 mainly influences Aβ deposition, while the effects on gray matter volume and glucose metabolism are at best subtle.


BACKGROUND
NCT01638949.
From INSERM (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.), U1077; Université de Caen Normandie, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.) and Ecole Pratique des Hautes Etudes, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.); and CHU de Caen, U1077 (J.G., E.M.A.-U., M.F., A.P., F.E., G.C.), Service de Biochimie (S.F.), and Service de Neurologie (V.d.L.S.), France. gonneaud@cyceron.fr.
Julie
J
Gonneaud
From INSERM (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.), U1077; Université de Caen Normandie, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.) and Ecole Pratique des Hautes Etudes, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.); and CHU de Caen, U1077 (J.G., E.M.A.-U., M.F., A.P., F.E., G.C.), Service de Biochimie (S.F.), and Service de Neurologie (V.d.L.S.), France.
Eider M
EM
Arenaza-Urquijo
From INSERM (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.), U1077; Université de Caen Normandie, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.) and Ecole Pratique des Hautes Etudes, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.); and CHU de Caen, U1077 (J.G., E.M.A.-U., M.F., A.P., F.E., G.C.), Service de Biochimie (S.F.), and Service de Neurologie (V.d.L.S.), France.
Marine
M
Fouquet
From INSERM (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.), U1077; Université de Caen Normandie, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.) and Ecole Pratique des Hautes Etudes, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.); and CHU de Caen, U1077 (J.G., E.M.A.-U., M.F., A.P., F.E., G.C.), Service de Biochimie (S.F.), and Service de Neurologie (V.d.L.S.), France.
Audrey
A
Perrotin
From INSERM (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.), U1077; Université de Caen Normandie, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.) and Ecole Pratique des Hautes Etudes, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.); and CHU de Caen, U1077 (J.G., E.M.A.-U., M.F., A.P., F.E., G.C.), Service de Biochimie (S.F.), and Service de Neurologie (V.d.L.S.), France.
Sabine
S
Fradin
From INSERM (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.), U1077; Université de Caen Normandie, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.) and Ecole Pratique des Hautes Etudes, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.); and CHU de Caen, U1077 (J.G., E.M.A.-U., M.F., A.P., F.E., G.C.), Service de Biochimie (S.F.), and Service de Neurologie (V.d.L.S.), France.
Vincent
V
de La Sayette
From INSERM (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.), U1077; Université de Caen Normandie, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.) and Ecole Pratique des Hautes Etudes, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.); and CHU de Caen, U1077 (J.G., E.M.A.-U., M.F., A.P., F.E., G.C.), Service de Biochimie (S.F.), and Service de Neurologie (V.d.L.S.), France.
Francis
F
Eustache
From INSERM (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.), U1077; Université de Caen Normandie, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.) and Ecole Pratique des Hautes Etudes, UMR-S1077 (J.G., E.M.A.-U., M.F., A.P., V.d.L.S., F.E., G.C.); and CHU de Caen, U1077 (J.G., E.M.A.-U., M.F., A.P., F.E., G.C.), Service de Biochimie (S.F.), and Service de Neurologie (V.d.L.S.), France.
Gaël
G
Chételat
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005026:Ethylene Glycols; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics; D009929:Organ Size; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D055815:Young Adult
D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D005026:Ethylene Glycols; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C545186:florbetapir; D005947:Glucose