Table 1. Mouse models utilized in the study.

Mouse genotype	Abbrev.	Age, weeks	Pathology/ Mitochondrial alterations	Ref.
Human APP (K670N, M671L) under the control of the hamster prion protein promoter	APP	10–20; 40–60	Aβ plaques by 44 weeks; oxidative lipid damage, astrogliosis and microgliosis. No tangles. Impaired cognitive function at 24–40 weeks. Reduced mitochondrial membrane potential, ATP, altered dynamics and hypometabolism detected before the onset of amyloid plaques. MOAS are observed at 10 weeks	14; 15; 41; 46; 48; 49
Human PSEN1 (M146L) driven by the rat PDGF-β promoter	PS1	10–20; 40	No abnormal pathology up to 2.5 years. Elevated Aβ42. Cognitive impairment after 48 weeks; Altered mitochondrial motility detected in embryonic neurons; loss of mitochondrial activity and altered brain energetics detected at 32 weeks. Low MOAS levels	42; 15
Human APP (K670N, M671L) crossed with PSEN1 (M146L). The two trans-genes segregate independently	APP/PS1	10–20; 40–60	Aβ accumulation at ~24 weeks. Dystrophic neurites and GFAP-positive astrocytes at ~24 weeks with later microglial activation. Progressive cognitive impairment starting at 24 weeks.Altered mitochondrial motility in embryonic neurons. Reduced mitochondrial membrane potential, ATP levels, altered dynamics and hypometabolism are detected before the onset of amyloid plaques. Substantial MOAS formation at 10 weeks	15; 43; 46
Human PSEN1 (PS1M146V), APP (K670N, M671L) and MAPT(P30IL) transgenes integrated at a single locus under the control of the mouse Thy1.2 promoter	3xTgAD	24; 40–60	Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 24 weeks. Extensive Aβ deposits and Tau pathology by 48 weeks. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles. Cognitive impairment by 16 weeks. Decreased mitochondrial respiration and pyruvate dehydrogenase protein level at 12 weeks. Increased hydrogen peroxide production and lipid peroxidation. Embryonic neurons exhibited significantly decreased mitochondrial respiration and increased glycolysis. MOAS formation at 24 weeks	35; 44; 47
Human Tau (P301S) under the direction of the mouse prion protein promoter.	Tau	40	Neuron loss, brain atrophy and neurofibrillary tangles by 32 weeks. Neuroinflammation with microgliosis and astrocytosis. Impairments in spatial memory and learning ability in Morris water maze. About 80 percent mortality by 12 months. Presence of mitochondrial dysfunction starting at 28 weeks: dysregulated mitochondrial enzymes; the reduction of complex V, ATP levels, and NADH-ubiquinone oxidoreductase activities. MOAS observed at 40 weeks	45; 50

APP: amyloid precursor protein; PSEN1: presenilins 1; PDGF: platelet-derived growth factor; MAPT: microtubule-associated protein tau; GFAP: glial fibrillary acidic protein; LTP: long-term potentiation.