Deposition of BACE-1 Protein in the Brains of APPPS1 Double Transgenic Mice

Abstract EN

The main causes of Alzheimer’s disease remain elusive.

Previous data have implicated the BACE-1 protein as a central player in the pathogenesis of Alzheimer’s disease.

However, many inhibitors of BACE-1 have failed during preclinical and clinical trials for AD treatment.

Therefore, uncovering the exact role of BACE-1 in AD may have significant impact on the future development of therapeutic agents.

Three- and six-month-old female APP/PS1 double transgenic mice were used to study abnormal accumulation of BACE-1 protein in brains of mice here.

Immunofluorescence, immunohistochemistry, and western blot were performed to measure the distributing pattern and expression level of BACE-1.

We found obvious BACE-1 protein accumulation in 3-month-old APP/PS1 mice, which had increased by the time of 6 months.

Coimmunostaining results showed BACE-1 surrounded amyloid plaques in brain sections.

The abnormal protein expression might not be attributable to the upregulation of BACE-1 protein, as no significant difference of protein expression was observed between wild-type and APP/PS1 mice.

With antibodies against BACE-1 and CD31, we found a high immunoreactive density of BACE-1 protein on the outer layer of brain blood vessels.

The aberrant distribution of BACE-1 in APP/PS1 mice suggests BACE-1 may be involved in the microvascular abnormality of AD.