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Basic Science and Pathogenesis.

Olga Minaeva1, Kevin P Kotredes2, Juliet A Moncaster1

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Environmental toxicants like lead, cadmium, and arsenic accumulate in the brain and blood of mice after chronic exposure. This study demonstrates their detection and mapping in brain regions, highlighting a link between toxicant exposure and Alzheimer's Disease risk.

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Area of Science:

  • Neuroscience
  • Environmental Health
  • Toxicology

Background:

  • Alzheimer's Disease (AD) and related dementias (ADRDs) are influenced by age, genetics, and environmental exposures.
  • Environmental toxicants, including lead (Pb), cadmium (Cd), and arsenic (As), pose significant public health risks, disproportionately affecting disadvantaged populations.
  • This research investigates the hypothesis that these neurotoxicants alter AD-linked gene expression and potentiate AD pathobiology.

Purpose of the Study:

  • To investigate the accumulation and regional distribution of lead (Pb), cadmium (Cd), and arsenic (As) in mouse brains following chronic exposure.
  • To utilize laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging for multi-elemental brain mapping and ultra-trace elemental quantification.
  • To establish a link between environmental toxicant exposure and potential Alzheimer's Disease pathobiology.

Main Methods:

  • MODEL-AD mice were exposed to Pb, Cd, or As in drinking water for 30 days.
  • Brain and blood samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) for elemental quantification.
  • LA-ICP-MS imaging was employed for precise anatomical localization and mapping of neurotoxicant accumulation in brain tissues.

Main Results:

  • Robust uptake of Pb, Cd, and As was observed in mouse brain and blood after 30-day exposure to epidemiologically relevant levels.
  • A strong correlation was found between brain and blood levels of As, Cd, and Pb.
  • LA-ICP-MS mapping revealed non-homogeneous, element-specific accumulation of neurotoxicants in distinct brain regions, including the hippocampus and cortex.

Conclusions:

  • MODEL-AD mice exposed to Pb, Cd, or As accumulate these neurotoxicants in blood and brain.
  • ICP-MS solution analysis and LA-ICP-MS imaging effectively detect, image, and quantify neurotoxicant accumulation.
  • Findings support the potential role of environmental toxicants in AD pathobiology, warranting further investigation.