Grant: CIHR Fellowship

Alzheimer's disease (AD) is a growing healthcare and social concern worldwide which affects 500,000 Canadians and, in the absence of effective therapies, is projected to affect 4 million by the year 2050. Recent evidence suggests that a protein called ATP-binding cassette transporter A1 (ABCA1), which acts as a membrane transporter for cholesterol in cells and is present in many cells in the body including the nerve and glial cells in brain, plays a beneficial role in AD by facilitating the clearance of the toxic amyloid beta peptides from the brain. We have recently found that ABCA1 in the brain, in addition to regulating cholesterol metabolism, also plays important role in neuroinflammation, which is an important factor in AD. Hence, we are interested in studying the specific role of brain ABCA1, specifically the distinct contribution of neuronal and astrocytic ABCA1, on the progression and severity of AD-like neuropathology in a transgenic mouse model of AD. In parallel, we will also explore the therapeutic potential of enhancing the expression of ABCA1 in brain as a means of reducing neuroinflammation and amyloid deposition in a mouse of AD. The findings from these studies will help us better understand the interplay of brain cholesterol and inflammation in AD pathogenesis, as well as provide further support for ABCA1 as a therapeutic target in AD.