Deposition of BACE-1 Protein in the Brains of APP/PS1 Double Transgenic Mice

Abstract

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.

Echinacoside Suppresses Amyloidogenesis and Modulates F-actin Remodeling by Targeting the ER Stress Sensor PERK in a Mouse Model of Alzheimer’s Disease

“…Figure 3A presents images of Aβ-plaque immunoreactivity in the hippocampus and cortex of the 4 groups, showing that 2 × Tg-AD mice at 10 months of age developed obvious Aβ-plaque deposition in both hippocampus and cortex. This AD-like pathogenesis was consistent with previous reports (Capell et al, 2000;Luo et al, 2016). Compared with vehicle-treated Non-Tg mice, quantitative analysis revealed that the vehicle-treated 2 × Tg-AD mice exhibited a significantly greater Aβ-plaque load in the hippocampus (Figure 3B, P < 0.001) and cortex ( Figure 3C, P < 0.001).…”

Cornuside Is a Potential Agent against Alzheimer’s Disease via Orchestration of Reactive Astrocytes

“…As a progressive condition of neurodegeneration featuring cognitive impairment, behavioral abnormalities, and neuropsychiatric indications [ 1 , 2 ], Alzheimer’s disease (AD) is the chief pathogenic factor of dementia, which has become one of the greatest burdens of the century. Currently, the number of people having AD is over 50 million worldwide and, by 2050, the number is estimated to become 100 million.…”

Examination of Longitudinal Alterations in Alzheimer’s Disease-Related Neurogenesis in an APP/PS1 Transgenic Mouse Model, and the Effects of P33, a Putative Neuroprotective Agent Thereon

“…Demars et al measured high APP protein levels in 2-month-old APP/PS1 animals [ 26 ], which agrees with our findings. Previous studies have shown that both the BACE1 protein level [ 80 ] and the enzymatic activity are elevated [ 81 ], and BACE1 is accumulated around plaques in AD models, independent of age [ 80 , 82 , 83 ]. We assume that changes in the amounts of products formed in the amyloidogenic pathway may support the hypothesis that the enhanced expression and/or activity of BACE1 is likely to contribute to the cleavage of APP, resulting in reduced APP and elevated C99 levels in Tg animals.…”