Background: The Apolipoprotein E (ApoE) alleles ɛ2, ɛ3, and ɛ4 are known to differentially modulate cerebral glucose metabolism and the risk for Alzheimer’s disease (AD) via both amyloid-β (Aβ)-dependent and independent mechanisms. Objective: We investigated the influence of ApoE on cerebral glucose metabolism in humanized APOE Targeted Replacement (TR) mice at ages that precede the comparison of Aβ parenchymal deposits in APOE4-TR mice. Methods: Fludeoxyglucose ([18F]FDG) positron emission tomography (PET) measures were performed longitudinally in homozygous APOE-TR mice (APOE2, APOE3, APOE4; n = 10 for each group) at 3, 5, 11, and 15 months. Results were quantified using standard uptake values and analyzed statistically using a linear mixed effects model. Levels of the Aβ40 and Aβ42 peptides were quantified ex vivo using enzyme-linked immunosorbent assay (ELISA) at 15 months in the same animals. Results:[...]
Differential Effect of APOE Alleles on Brain Glucose Metabolism in Targeted Replacement Mice: An [18F]FDG-μPET Study
Frumento, Paolo;
2017-01-01
Abstract
Background: The Apolipoprotein E (ApoE) alleles ɛ2, ɛ3, and ɛ4 are known to differentially modulate cerebral glucose metabolism and the risk for Alzheimer’s disease (AD) via both amyloid-β (Aβ)-dependent and independent mechanisms. Objective: We investigated the influence of ApoE on cerebral glucose metabolism in humanized APOE Targeted Replacement (TR) mice at ages that precede the comparison of Aβ parenchymal deposits in APOE4-TR mice. Methods: Fludeoxyglucose ([18F]FDG) positron emission tomography (PET) measures were performed longitudinally in homozygous APOE-TR mice (APOE2, APOE3, APOE4; n = 10 for each group) at 3, 5, 11, and 15 months. Results were quantified using standard uptake values and analyzed statistically using a linear mixed effects model. Levels of the Aβ40 and Aβ42 peptides were quantified ex vivo using enzyme-linked immunosorbent assay (ELISA) at 15 months in the same animals. Results:[...]I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.