Alzheimer’s disease (AD) has been associated with changes in metabolic function and synaptic dysfunction. How synaptic metabolism is modified in AD is under-explored. To address this gap, we are investigating synaptic mitochondrial function in the TgF344-AD rat model of AD. This model expresses mutant human amyloid precursor protein and human presenilin 1 with Δexon9 mutation; both driven by a mouse prion promoter. A three factor design was employed, with age (7- or 15-months), genotype (wild-type or mutant) and brain region (frontal cortex, auditory cortex, hippocampus, superior colliculus, inferior colliculus and cerebellum) as factors. Fresh brains were extracted and the above brain regions and dissected. Each brain region was homogenised in 0.32M sucrose and 10mM Tris-Cl buffer and then centrifuged multiple times at 4°C to extract synaptosomes. Protein content was estimated with a BCA assay. 5µg of protein per brain region was subject to analyses. A Seahorse XF Cell Mito Stress Test Kit was used in conjunction with a Seahorse XFP flux analyser (both Agilent) to measure i) basal oxidative consumption rate, ii) proton leak, iii) maximum respiration, iv) spare respiratory capacity, v) non-mitochondrial oxygen consumption, vi) ATP production, and vii) coupling efficiency (all n=6 except wild-type 7-months, for which n=3). Three-way ANOVAs found a possible real effect of greater coupling efficiency in wild-type (7-months mean=24.3%, standard deviation ±15.0; 15-months mean=20.2, ±17.8) than mutant (7-months mean=15.4, ±17.4; 15-months mean=5.2, ±12.0) (genotype factor P<0.05) and trends toward more non-mitochondrial oxygen consumption, spare respiratory capacity and proton leak in mutant rats. We also prepared a separate sample of synaptosomes for scanning electron microscopy, following glutaradehyde fixation and gold sputter coating. Micrographs were collected from all samples on a Zeiss Supra 40VP microscope. Synaptosome perimeter measures were performed in ImageJ. Preliminary findings lacked evidence of morphological differences between groups. Synaptosomes ranged in perimeter from 2.7µm in inferior colliculus to 10.1µm in hippocampus. Taken together, these data suggest potential differences in aspects of synaptic mitochondrial function relating to genotype in the TgF344-AD rat. Future work will expand on these data to provide greater statistical power and will furthermore employ correlative PET imaging and molecular biological approaches.