Aβ(42) induced MRI changes in aged rabbit brain resembles AD brain

B N Ramesh1, K P Raichurkar, N M Shamasundar

  • 1Department of Biochemistry and Nutrition, CFTRI, Mysore, India.

Insights

Amyloid-beta (Aβ) injections in aged rabbits caused brain atrophy, particularly in the frontal lobe and hippocampus, mirroring changes seen in human Alzheimer's disease (AD) brains. This suggests Aβ plays a key role in AD-related neurodegeneration.

Area of Science:

  • Neuroscience
  • Neurodegenerative Diseases
  • Biomedical Imaging

Background:

  • Alzheimer's disease (AD) is a leading cause of dementia, characterized by brain atrophy and volume loss.
  • Amyloid-beta (Aβ) deposition is a key pathological hallmark of AD and is correlated with brain atrophy.
  • Structural brain imaging, such as Magnetic Resonance Imaging (MRI), is crucial for assessing neuroanatomical alterations.

Purpose of the Study:

  • To investigate the causal role of Aβ in inducing brain structural changes.
  • To compare Aβ-induced neuroanatomical alterations in an aged rabbit model with human AD brain changes.
  • To elucidate the specific brain regions affected by Aβ deposition using MRI.

Main Methods:

  • Chronic intracerebral injection of Aβ(1-42) or saline into aged rabbits (n=10 per group).
  • Serial MRI scans were performed before and 45 days after injection to measure brain structure.
  • Comparative MRI analysis was conducted on human AD patients (n=10) and healthy controls (n=10).

Main Results:

  • Aβ(1-42) injection in rabbits led to significant reductions in frontal lobe and hippocampus thickness, and increased lateral ventricle volume.
  • Human AD brains showed significant reductions in frontal lobe and hippocampus thickness compared to controls.
  • Brain atrophy patterns in the frontal lobe and hippocampus of rabbits correlated with those observed in human AD brains.

Conclusions:

  • Aβ(1-42) administration induces structural brain changes in rabbits that partially mimic human Alzheimer's disease.
  • The frontal lobe and hippocampus are critical regions affected by Aβ-induced neurodegeneration in both rabbits and humans.
  • The aged rabbit model provides a valuable platform for studying Aβ-related brain atrophy and potential therapeutic interventions for AD.