Distribution of Copper, Iron, and Zinc in the Retina, Hippocampus, and Cortex of the Transgenic APP/PS1 Mouse Model of Alzheimer's Disease.
Seyed Mostafa Hosseinpour MashkaniDavid P BishopNewsha Raoufi-RadPaul A AdlardOlga ShimoniSeyyed Mojtaba GolzanPublished in: Cells (2023)
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-β 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.
Keyphrases
- diabetic retinopathy
- optic nerve
- cerebral ischemia
- wild type
- mass spectrometry
- functional connectivity
- mouse model
- resting state
- heavy metals
- high resolution
- type diabetes
- subarachnoid hemorrhage
- optical coherence tomography
- oxide nanoparticles
- high fat diet induced
- white matter
- human health
- cognitive decline
- health risk assessment
- transition metal
- health risk
- oxidative stress
- metabolic syndrome
- insulin resistance
- skeletal muscle
- climate change
- high performance liquid chromatography
- ms ms
- cerebrospinal fluid