The amyloid-β pathway in Alzheimer's disease: a plain language summary.

What is this summary about?: This plain language summary of an article published in Molecular Psychiatry, reviews the evidence supporting the role of the amyloid-β (Aβ) pathway and its dysregulation in Alzheimer's disease (AD), and highlights the rationale for drugs targeting the Aβ pathway in the early stages of the disease.

Why is this important?: Aβ is a protein fragment (or peptide) that exists in several forms distinguished by their size, shape/structure, degree of solubility and disease relevance. The accumulation of Aβ plaques is a hallmark of AD. However, smaller, soluble aggregates of Aβ - including Aβ protofibrils - also play a role in the disease. Because Aβ-related disease mechanisms are complex, the diagnosis, treatment and management of AD should be reflective of and guided by up-to-date scientific knowledge and research findings in this area. This article describes the Aβ protein and its role in AD, summarizing the evidence showing that altered Aβ clearance from the brain may lead to the imbalance, toxic buildup and misfolding of the protein - triggering a cascade of cellular, molecular and systematic events that ultimately lead to AD.

What are the key takeaways?: The physiological balance of brain Aβ levels in the context of AD is complex. Despite many unanswered questions, mounting evidence indicates that Aβ has a central role in driving AD progression. A better understanding of the Aβ pathway biology will help identify the best therapeutic targets for AD and inform treatment approaches.