Alzheimer's disease and transgenic mice

Area of Science:

• Neuroscience
• Genetics
• Animal Models

Background:

• Alzheimer's disease (AD) and Down syndrome (DS) are linked to amyloid precursor protein (APP) deposition.
• Transgenic animal models are crucial for studying AD and DS pathogenesis.
• Understanding APP's role requires models that express its major neuronal isoforms.

Purpose of the Study:

• To create transgenic mice overexpressing human APP isoforms (APP695, APP751, APP770).
• To investigate if APP overexpression can induce AD and DS-like pathology.
• To analyze behavioral changes in mice with altered APP levels.

Main Methods:

• Generation of transgenic mice using the metallothionin promoter to drive APP isoform expression.
• Quantification of transgenic APP expression in various tissues, including the brain.
• Assessment of cognitive and motor functions using spatial navigation and motor behavior tasks.

Main Results:

• Transgenic mice expressed human APP isoforms in multiple tissues, including the brain.
• Expression levels of transgenic APP did not surpass endogenous mouse APP levels.
• No pathological hallmarks of AD or DS were observed in the transgenic mice.
• Significant alterations in spatial navigation and motor behavior were detected.

Conclusions:

• Overexpression of human APP isoforms in mice did not replicate the core neuropathology of AD or DS.
• Transgenic mice exhibited behavioral deficits, suggesting APP's role in neural function.
• The sufficiency of APP overexpression alone in inducing Alzheimer's pathology remains undetermined.