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Anton, P.

Publications and source records attributed to Anton, P..

2 recordsLinked to original sources

Binding of Monomeric and Polymeric Alzheimers Aβ peptides to Exosomes

Exosomes are secreted by every cell in our body under both physiological and pathological conditions. They travel in the blood, CSF, and all studied biofluids. Their biological roles have been reported to include delivery of important physiological cargo between organs and cells, clearance of toxic proteins; maintenance of cellular stasis, and the propagation of disease pathology. In the case of Alzheimers disease (AD) exosomes have been shown to carry pathological proteins such as amyloid, yet the specificity of this association of amyloid and exosomes is unclear. To address this deficiency, we utilized Isothermal Titration Calorimetry (ITC) to measure the binding of amyloid to exosomes. Here we report that A{beta}40 and A{beta}42 bind to exosomes in a saturable and endothermic manner, a phenomenon not observed with the scrambled versions of either peptide. This points to this interaction being more specific than previously understood, and to amyloid associated with exosomes as an important pool of this peptide in the plasma.

neuroscience

Pro-inflammatory Cytokine GM-CSF Improves Learning/Memory and Brain Pathology in Dp16 Down Syndrome Mice and Improves Learning/Memory in Wild-Type Mice

Down syndrome (DS) is characterized by chronic neuroinflammation, peripheral inflammation, astrogliosis, imbalanced excitatory/inhibitory neuronal function, and cognitive deficits in both humans and mouse models. Suppression of inflammation has been proposed as a therapeutic approach to treating DS co-morbidities, including intellectual disability (DS/ID). Conversely, we discovered previously that treatment with the pro-inflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) improved cognition and reduced biomarkers of brain pathology in humans with Alzheimers disease (AD), another inflammatory disorder, and in a mouse model of AD. To investigate the effects of GM-CSF treatment on DS/ID, we assessed behavior and brain pathology in 12-14 month-old DS mice (Dp[16]1Yey) and their wild-type (WT) littermates, neither of which develop amyloid, and found that GM-CSF treatment improved performance in the radial arm water maze in both Dp16 and WT mice compared to placebo. Dp16 mice also showed abnormal astrocyte morphology and aggregation and fewer calretinin-positive interneurons, both of which were improved by GM-CSF treatment. These findings suggest that stimulating and/or modulating inflammation and the innate immune system with GM-CSF treatment may enhance cognition in both people with DS/ID and in the typical aging population.

neuroscience