Histological Analysis of Beta-Amyloid (Aβ) and Metal Ion Aggregation into Neuritic Plaques in Tg2576 Transgenic Mice




Brown, Everett-Teejay

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Alzheimer’s disease (AD) is a neurodegenerative disease that affects cognition, behavior, and function. AD is considered a growing health concern because the number of patients with AD doubles every five years after age 65. AD is characterized by two types of lesions in the brain: intraneuronal neurofibrillary tangles and extracellular neuritic (senile) amyloid plaques--the plaques are an accumulation of β-amyloid (Aβ). There is considerable evidence suggesting that metals play a critical role in aggregating Aβ into neuritic plaques. Studies examining the role of metals in formulating Aβ plaque complexes have produced varying results. Further investigation into the role of metals in plaque formation might help uncover possible treatment interventions. The current study examines brain tissue from the Tg2576 transgenic mice model. The Tg2576 model is considered a staple in AD-related studies, and it is the most widely used model of AD in the world. In the current study, Tg2576 mice were split into groups and administered lab water, 10ppm zinc (Zn) water, 10ppm iron (Fe) water, or 10ppm zinc and copper (Cu) water. In AD, amyloid plaque congregation has been studied throughout the brain, including in transition cortex, piriform cortex, hippocampus, neocortex, amygdala nuclei, and basal ganglia. These brain regions are most commonly associated with learning and memory. Plaque-containing brain tissue from each of these regions was analyzed in Tg2576 mice using BioQuant. Plaque burden was assessed using three measurement parameters: normalized area, average area, and plaque number. Results showed that overall plaque burden was highest in the brains of animals raised on Zn and Zn + Cu water and highest in the cortical areas (transition & piriform cortex followed by neocortex). Plaque burden was less in the brains of mice raised on Fe water and less in the basal ganglia. The effects of metal type and brain region appeared to be independent.



Amyloid, Alzheimer's disease, Plaques, Metal ions, Tg2576, Transgenic mice