Compromised hemodynamic response in amyloid precursor protein transgenic mice

Area of Science:

• Neuroscience
• Biomedical Imaging
• Genetics

Background:

• Alzheimer's disease (AD) is characterized by amyloid plaques and vascular pathologies.
• APP23 transgenic mice overexpress amyloid precursor protein (APP751), recapitulating key AD neuropathologies.
• Assessing brain functionality in AD models is crucial for understanding disease mechanisms.

Purpose of the Study:

• To investigate brain functionality in APP23 transgenic mice using functional magnetic resonance imaging (fMRI).
• To characterize the cerebrovascular reactivity and hemodynamic response in a mouse model of Alzheimer's disease.

Main Methods:

• APP23 transgenic mice and age-matched wild-type littermates were used.
• Functional magnetic resonance imaging (fMRI) was employed for brain activity assessment.
• Pharmacological stimulation with bicuculline (GABA(A) antagonist) and acetazolamide (vasodilator) was performed.

Main Results:

• Aged APP23 mice exhibited a significantly reduced cerebral hemodynamic response to bicuculline compared to wild-type controls.
• Compromised cerebrovascular reactivity was indicated by reduced responsiveness to acetazolamide in APP23 mice.
• fMRI demonstrated sensitivity in detecting functional deficits in this Alzheimer's disease mouse model.

Conclusions:

• fMRI is a valuable tool for phenotyping genetically engineered animals modeling Alzheimer's disease.
• APP23 mice display impaired brain hemodynamic responses and cerebrovascular reactivity.
• These findings contribute to understanding functional changes in Alzheimer's disease pathogenesis.