Table 2 Selected studies in which the effect of the APOE genotype on mitochondrial function-related traits was investigated. Only studies were included in which effects of APOE4 were compared with those of APOE3
Reference | Model system | Main findings; APOE4 vs. APOE3 |
|---|---|---|
Mosconi et al. [88, 89]; Langbaum et al. [90]; Small et al. [91, 93]; Reiman et al. [92, 94–96] | Human subjects with and without diagnosed AD (brain) | -Glucose hypometabolism |
Xu et al. [105] | Hippocampi of human APOE ε3/ε3 and APOE ε4/ε4 AD patients | -Mitochondrial oxidative phosphorylation and energy metabolism ↓ |
Turchan-Cholewo et al. [173] | Human neuronal cultures | -GSH concentrations and mitochondrial membrane potential after treatment with HIV protein and opiate ↓ No effect in astrocytes. |
Valla et al. [174] | Young APOE ε4 carriers and non-carriers (posterior cingulate cortex tissue) | -CIV activity ↓ |
Chen et al. [87] | Primary neurons from NSE-APOE transgenic mice (cortex) Primary astrocytes from GFAP-APOE transgenic mice (cortex) Neuro-2A cells stably expressing APOE3 and APOE4, resp. | -Protein levels CI-V ↓ -Protein levels CI-V ↔ -Protein levels CI, CIV and CV ↓ -mRNA expression CIV subunit 1, CV subunit α ↓, Vdac1 ↑ -Activity CIV↓, citrate synthase ↔ -Mitochondrial respiratory capacity ↓ APOE4-R61T mutation or GIND24 treatment abolished detrimental effects on mitochondria. |
James et al. [106] | Mitochondrial fractions (hippocampus) from APOE transgenic mice | -Differential regulation of TCA cycle, ETC and ATP synthesis |
Liraz et al. [108] | Young APOE TR mice (4 months old, hippocampal neurons) | -Protein expression Tomm40, CIV subunit 1 ↓ |
Chin et al. [109] | Old APOE TR mice (15 months old, cortex) | -ATP levels ↓ -mRNA expression Ppargc1a, Gabpa ↓ |
Shi et al. [107] | Mitochondrial fractions (synaptosomes) from GFAP-APOE transgenic mice | -Pathways TCA, ETC, oxidation reduction ↓ -ATP synthesis ↓ -GSSG, MDA ↑ Effect stronger in presence of female gender. No effect in non-synaptic mitochondria. |
Tambini et al. [175] | Human fibroblasts treated with astrocyte-conditioned media obtained from APOE4 and APOE3 TR mice, resp. | -MAM activity ↑ |