Abstract
Alzheimer’s disease is associated with the production of Cu rich aβ fibrils. Because monitoring the changes in Cu level of organs has been proposed to follow the evolution of the disease, we analyzed the copper isotopic composition of serum and brain of APPswe/PSEN1dE9 transgenic mice, a model of Alzheimer’s disease, and wild-type (WT) controls. Serum composition of 3, 6, 9 and 12-month-old mice, as well as the composition of 9 brains of 12-month-old mice are reported. In WT mice, brains were ~1‰ isotopically heavier than serum, and the Cu isotopic composition of the serum was isotopically different between males and females. We propose that this effect of sex on the Cu isotopic budget of the serum may be related to a difference of Cu speciation and relative abundance of Cu carriers. Brains of APPswe/PSEN1dE9 mice were slightly lighter than brains of WT mice, while not statistically significant. This trend may reflect an increase of Cu(I) associated with the formation of Aβ fibrils. The Cu isotopic composition of the brains and serum were correlated, implying copper transport between these two reservoirs, in particular a transfer of Cu(I) from the brain to the serum. Altogether, these data suggest that Cu stable isotopic composition of body fluid may have the potential to be used as detection tools for the formation of Aβ fibrils in the brain, but further work has to be done.
Highlights
To cite this version: Frédéric Moynier, John Creech, Jessica Dallas, Marie Le Borgne
The major physiological features of Alzheimer’s disease (AD) are the formation of neurofibrillary tangles by neuronal accumulations of abnormal hyperphosphorylated tau filaments and the formation of senile plaques by extracellular deposits of amyloid β (Aβ) fibrils, mostly the 1 to 42 peptide (Aβ1-42)
We investigated if AD would lead to a different copper isotopic composition in serum and/or brain by analyzing the isotopic composition of organs from the APPswe/PSEN1dE9 transgenic mouse model
Summary
To cite this version: Frédéric Moynier, John Creech, Jessica Dallas, Marie Le Borgne. Serum and brain natural copper stable isotopes in a mouse model of Alzheimer’s disease. Brains of APPswe/PSEN1dE9 mice were slightly lighter than brains of WT mice, while not statistically significant This trend may reflect an increase of Cu(I) associated with the formation of Aβ fibrils. The Cu isotopic composition of the brains and serum were correlated, implying copper transport between these two reservoirs, in particular a transfer of Cu(I) from the brain to the serum These data suggest that Cu stable isotopic composition of body fluid may have the potential to be used as detection tools for the formation of Aβ fibrils in the brain, but further work has to be done. Diagnosis of AD is a major challenge and current work focuses on the detection of excess of total tau and Aβ in cerebrospinal fluid, and on using imaging of the brain by positron emission tomography and magnetic resonance imaging (MRI) for Aβ plaques (e.g. refs[2,3,4])
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