Targeting Apolipoprotein E for Alzheimer’s Disease:An Industry Perspective复制标题

靶向载脂蛋白E治疗阿尔茨海默病: 行业观点

Alzheimer’s disease (AD) is the leading cause of dementia in elderly people. Hallmarks of the disease include the deposition of amyloid beta (Aβ) plaques and the presence of neurofibrillary tangles. Thus, strategies that have gained the most traction in the field are predominantly focused on targeting amyloid and tau proteins. However, Alois Alzheimer also reported the presence of “adipose inclusions” as one of the pathologies in the AD brain, in addition to amyloid and tau, suggesting that AD brains display signs of aberrant lipid metabolism. Emerging data clearly indicate a strong link between AD and lipids. In fact, the brain is the most lipid-rich organ in the body and—despite accounting for about 2.1% of the total body weight—contains about 25% of total body sterols. In the central nervous system (CNS), lipids play a critical role in both structure and function. For example, unesterified cholesterol plays a specialized role as the major architectural component of the myelin sheath. In fact, about 70% of total brain cholesterol is present in the myelin sheath. The remaining lipids are present in functionally active pools in neurons and glia. During CNS development, required cholesterol and lipid pools are obtained exclusively from de novo synthesis. Whether there is any influence of plasma lipids on the brain lipid pool is currently unknown. Given such a crucial role of lipids in the CNS, maintaining lipid homeostasis in the brain is critical for maintaining a healthy state.

译文