Distribution of Copper, Iron, and Zinc in the Retina, Hippocampus, and Cortex of the Transgenic APP/PS1 Mouse Model of Alzheimer's Disease

A mis-metabolism of transition metals (i.e., copper, iron, and zinc) in the brain has been recognised as a precursor event for aggregation of Amyloid-beta plaques, a pathological hallmark of Alzheimer's disease (AD). However, imaging cerebral transition metals in vivo can be extremely challenging. As the retina is a known accessible extension of the central nervous system, we examined whether changes in the hippocampus and cortex metal load are also mirrored in the retina. Laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) was used to visualise and quantify the anatomical distribution and load of Cu, Fe, and Zn in the hippocampus, cortex, and retina of 9-month-old Amyloid Precursor Protein/Presenilin 1 (APP/PS1, n = 10) and Wild Type (WT, n = 10) mice. Our results show a similar metal load trend between the retina and the brain, with the WT mice displaying significantly higher concentrations of Cu, Fe, and Zn in the hippocampus (p < 0.05, p < 0.0001, p < 0.01), cortex (p < 0.05, p = 0.18, p < 0.0001) and the retina (p < 0.001, p = 0.01, p < 0.01) compared with the APP/PS1 mice. Our findings demonstrate that dysfunction of the cerebral transition metals in AD is also extended to the retina. This could lay the groundwork for future studies on the assessment of transition metal load in the retina in the context of early AD.

Automated summary

A mis-metabolism of transition metals in the brain has been recognized as a precursor event for aggregation of Amyloid-beta plaques in Alzheimer's disease. This study examined whether changes in the metal load in the hippocampus and cortex are also reflected in the retina, which is an accessible extension of the central nervous system.