Selective Serotonin Reuptake Inhibitors (SSRIs) may hold therapeutic benefits for people with Alzheimer’s disease (AD). SSRIs may perturb AD progression, or the conversion from MCI to AD, via increased neurogenesis, reduced oxidative... more
Selective Serotonin Reuptake Inhibitors (SSRIs) may hold therapeutic benefits for people with Alzheimer’s disease (AD). SSRIs may perturb AD progression, or the conversion from MCI to AD, via increased neurogenesis, reduced oxidative stress and/or favourable Amyloid-β Precursor Protein (AβPP) processing. This study used iPSC derived cortical neuronal cells carrying 3 different PSEN1 mutations, to investigate the effect of treatment with the SSRI, Citalopram on AβPP processing and oxidative stress. Control and PSEN1 mutation (L286V, A246E, M146L) iPSC-derived neurons were treated with Citalopram for 45 days. ADAM10 activity, AβPP processing and Aβ generation was measured in addition to cellular redox status. Citalopram treatment reduced the Aβ1-42:40 ratio in control but not in fAD PSEN1 cells. ADAM10 activity was increased with Citalopram treatments in fAD PSEN1 cell lines, which was also seen for sAβPPα secretion. Lower superoxide generation in fAD PSEN1 cells following Citalopram ...
Much of the early research into AD relies on a neuron-centric view of the brain, however, evidence of multiple altered cellular interactions between glial cells and the vasculature early in AD has been demonstrated. As such, alterations... more
Much of the early research into AD relies on a neuron-centric view of the brain, however, evidence of multiple altered cellular interactions between glial cells and the vasculature early in AD has been demonstrated. As such, alterations in astrocyte function are widely recognized a contributing factor in the pathogenesis of AD. The processes by which astrocytes may be involved in AD make them an interesting target for therapeutic intervention, but in order for this to be most effective, there is a need for the specific mechanisms involving astrocyte dysfunction to be investigated. “α disintegrin and metalloproteinase” 10 (ADAM10) is capable of proteolytic cleavage of the amyloid precursor protein which prevents amyloid-β generation. As such ADAM10 has been identified as an interesting enzyme in AD pathology. ADAM10 is also known to play a role in a significant number of cellular processes, most notable in notch signaling and in inflammatory processes. There is a growing research bas...
Altered energy metabolism in Alzheimer’s disease (AD) is considered a major pathological hallmark implicated in the early stages of the disease process. Astrocytes play a central role in brain homeostasis and are increasingly implicated... more
Altered energy metabolism in Alzheimer’s disease (AD) is considered a major pathological hallmark implicated in the early stages of the disease process. Astrocytes play a central role in brain homeostasis and are increasingly implicated in multiple neurodegenerative diseases. We report that astrocytes differentiated from early onset familial Alzheimer’s disease (fAD) patients or control cells treated with Amyloid β oligomers exhibit significant changes in their metabolism including glucose uptake, glutamate uptake and lactate release, with increases in oxidative and glycolytic metabolism. Furthermore, we demonstrate evidence of gliosis in fAD astrocytes in addition to a change in metabolic pathways including glutamate, purines, arginine, and the citric acid cycle. Homeostatic responses to brain activity and cellular metabolism are central to normal brain function. However, altered brain metabolism and cellular stress present significant risk factors for the onset and progression of ...
