Amyloid-Beta42 Structure Unravels its Aggregation and Toxicity in Alzheimer’s Disease

Amyloid-Beta42 Structure Unravels its Aggregation and Toxicity in Alzheimer’s Disease
In a new study entitled “Aβ(1–42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer's disease,” researchers established the molecular structure of a key form of amyloid-β (Aβ) protein, Aβ42. This finding allows researchers to understand how Aβ42 accumulates in plaque aggregates in the brain of Alzheimer's patients, bringing them closer to devising strategies to counteract its toxicity. The study was published in in the journal Nature Structural & Molecular Biology. In this study, researchers at the University of Illinois at Chicago determined the molecular structure of Aβ42, one of the forms of the amyloid-β (Aβ) protein (the second form is Aβ40), the protein advanced as a key determinant of Alzheimer's disease. Increasing reports establish Aβ42 accumulation in the brain as the determinant event triggering Alzheimer's disease cascade, rather than Aβ40. Notably, however, the structural architecture of Aβ42 has remained unknown but it is a crucial piece of the puzzle to understand how it aggregates into toxic plaques, a hallmark of Alzheimer’s. It was discovered that the accumulation of Aβ42 in brain plaques occurs in an "S" pattern, piling on each other as layers, forming triple flat structures (known as beta sheets). They found also that Aβ42 forms a "salt bridge," i.e. a connection between positive- and negative-charged molecules, with its last amino acid th
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