Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal18F-FDG and18F-DPA-714 PET imaging.
Preclinical animal model studies of brain energy metabolism and neuroinflammation in Alzheimer's disease have produced conflicting results, hampering both the elucidation of the underlying disease mechanism and the development of effective Alzheimer's disease therapies. Here, we aimed to quantify the relationship between brain energy metabolism and neuroinflammation in the APP/PS1-21 transgenic mouse model of Alzheimer's disease using longitudinal in vivo18F-FDG and18F-DPA-714) PET imaging and ex vivo brain autoradiography. APP/PS1-21 (TG, n = 9) and wild type control mice (WT, n = 9) were studied longitudinally every third month from age 6 to 15 months with18F-FDG and18F-DPA-714 with a one-week interval between the scans. Additional TG (n = 52) and WT (n = 29) mice were used for ex vivo studies. In vivo, the18F-FDG SUVs were lower and the18F-DPA-714 binding ratios relative to the cerebellum were higher in the TG mouse cortex and hippocampus than in WT mice at age 12 to 15 months ( p < 0.05). The ex vivo cerebellum binding ratios supported the results of the in vivo18F-DPA-714 studies but not the18F-FDG studies. This longitudinal PET study demonstrated decreased energy metabolism and increased inflammation in the brains of APP/PS1-21 mice compared to WT mice.
1 MediCity Research Laboratory, University of Turku, Turku, Finland.|2 Turku PET Centre, University of Turku, Turku, Finland.
Jatta S
JS
Takkinen
1 MediCity Research Laboratory, University of Turku, Turku, Finland.|2 Turku PET Centre, University of Turku, Turku, Finland.
Francisco R
FR
López-Picón
1 MediCity Research Laboratory, University of Turku, Turku, Finland.|2 Turku PET Centre, University of Turku, Turku, Finland.
Rana
R
Al Majidi
2 Turku PET Centre, University of Turku, Turku, Finland.
Olli
O
Eskola
2 Turku PET Centre, University of Turku, Turku, Finland.
Anna
A
Krzyczmonik
2 Turku PET Centre, University of Turku, Turku, Finland.
Thomas
T
Keller
3 The Department of Biostatistics, University of Turku, Turku, Finland.
Eliisa
E
Löyttyniemi
2 Turku PET Centre, University of Turku, Turku, Finland.|4 Turku PET Centre, Åbo Akademi University, Turku, Finland.|5 Department of Chemistry, University of Turku, Turku, Finland.
Olof
O
Solin
6 Turku PET Centre, Turku University Hospital, Turku, Finland.|7 Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.
Juha O
JO
Rinne
1 MediCity Research Laboratory, University of Turku, Turku, Finland.|2 Turku PET Centre, University of Turku, Turku, Finland.
Merja
M
Haaparanta-Solin
D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D004660:Encephalitis / Q000000981:diagnostic imaging / Q000378:metabolism; D004734:Energy Metabolism; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography / Q000379:methods*; D053764:Presenilin-1 / Q000235:genetics; D011720:Pyrazoles; D011743:Pyrimidines
D016564:Amyloid beta-Protein Precursor; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D053764:Presenilin-1; D011720:Pyrazoles; D011743:Pyrimidines; C047515:2-fluoro-2-deoxyglucose-6-phosphate; D019298:Glucose-6-Phosphate
18F-DPA-714; 18F-FDG; Alzheimer’s disease; PET; longitudinal imaging