Targeting Blood-Brain Barrier Dysfunction: A Therapeutic Approach in the Treatment of Alzheimer’s Disease

With the long-term care costs for people living with Alzheimer’s disease (AD) and other dementias estimated to increase to $16.9 trillion and 115.8 million disability-adjusted life years (DALYs) lost annually by 2050, the human toll of this devastating neurodegenerative disorder is immeasurable. Prominent research has identified blood-brain barrier (BBB) dysfunction, triggered by neurotoxic amyloid-beta (Aβ) accumulation, as a critical biomarker in the onset and progression of AD. Its interference with the expression of key receptor and transporter proteins in the BBB may accelerate the formation of neuritic plaques and neurofibrillary tangles, leading to progressive neurological decline. Investigating BBB dysfunction and abnormal expression of receptor and transporter proteins—including LRP-1, GLUT-1, Pgp, and RAGE—may lead to early diagnosis of the disease, which is critical to monitoring and administering treatment to slow the decline in cognitive abilities of AD patients. This investigation attempts to determine the viability of current interventions that aim to address the cycle of Aβ accumulation and BBB dysfunction by regulating LRP-1, GLUT-1, Pgp, and RAGE. Exploring BBB receptors and transporters as key therapeutic targets may play a critical role in addressing the cycle of Aβ aggregation and BBB dysfunction, allowing researchers to discover clinical interventions to treat the pathology and progression of Alzheimer’s disease in the human clinical context.