A Better AD Model

Fifty million people live with dementia around the globe – approximately two thirds of which suffer from Alzheimer’s disease. Driven by an aging population, this daunting figure is expected to exceed 152 million by 2050. The potential economic impact? The World Alzheimer Report 2018 makes for a worrying read: care for dementia currently exceeds $1 trillion a year – a figure that is forecast to double by 2030 (1). The report called for significant investment in the field and, in response, the G8 countries committed to developing a dementia cure or treatment by 2025. How? By collectively increasing funding for dementia research, calling for greater innovation, and recognizing dementia as a growing threat to global health.

Despite being described over a century ago, we are only now beginning to understand the molecular mechanisms that underpin AD pathology (2). In Alzheimer’s patients, abnormal aggregates of the protein amyloid beta (Aβ) – the hallmark of the disease – can be seen at the microscopic level (3); yet, the hypothesis that amyloid accumulation is the major cause of neurodegeneration has come under increasing scrutiny. Now, evidence suggests that prefibrillar soluble Aβ oligomers are more toxic to neurons, and inhibit many important neuronal activities that relate to the symtoms of AD (4).