Transgenic mice expressing the amyloid β protein-containing carboxyl-terminal fragment of the Alzheimer amyloid precursor protein

Abstract

The deposition of amyloid β protein (Aβ) in the brain is one of the main pathological features of Alzheimer's disease (AD). Aβ is derived from the amyloid precursor protein (AβPP). It was shown that the carboxyl-terminal 100 residues of AβPP containing the Aβ sequence could form amyloid-like fibrils, and could be neurotoxic in vitro. To investigate the relationship between this fragment and amyloidogenesis in vivo, we developed transgenic mice expressing the Aβ-containing carboxylterminal fragment under the control of the neuron specific enolase promoter. In these mice, the mRNA from the transgene was expressed at a substantial level in the brain. However, immunohistochemical studies of the brains did not show any pathologic changes. These results suggest that the expression of the Aβ containing carboxyl-terminal fragment itself may not directly lead to AD-like neuropathologic changes in vivo.

Key Words:

• ALZHEIMER'S DISEASE (AD)
• AMYLOID PRECURSOR PROTEIN (AβPP)
• AMYLOID β PROTEIN
• TRANSGENIC MICE
• NEURON SPECIFIC ENOLASE
• NEURON SPECIFIC ENOLASE (NSE) PROMOTER