Alzheimer’s is currently an irreversible brain disorder that affects memory, cognitive skills and eventually the ability to carry out even simple tasks. The cause of Alzheimer’s disease, which is the most common form of dementia, affects an estimated 44 million worldwide. While Alzheimer’s is not yet fully understood, Amyloid β-Protein (Aβ) is known to play a key role. In the case of Alzheimer’s disease, Aβ is thought to form plaques that build up in the brain resulting from the formation of aggregating fibrils.

Research led by Lothar Gremer at the Institute of Complex Systems, has unveiled a new high-resolution structure of Amyloid β-Protein (1-42) using both cryo-electron microscopy (cryo-EM) and nuclear magnetic resonance (NMR). Unlike preceding structures, conditions with a low pH were used which resulted in a new polymorph that was not previously seen. Nearly all of the R-groups are well-resolved and binding sites for monomeric Aβ were identified.  They also surmise that one mutant form, A2T (Icelandic), may disrupt fibril stability due to a more polar Threonine in place of the Alanine in the second position; whereas, A2V has a nonpolar Valine substitution which supports fibril stability. The hope is that the new structure and insight can lead to research into disrupting fibril formation, and ultimately a successful Alzheimer’s treatment. ^1,2

While there is currently no cure for Alzheimer’s disease, there is much optimism that a preventative treatment or cure may one day exist with the continued research around Aβ 1-42 and other related fragments.

References:

1. http://www.alzforum.org/news/research-news/amyloid-v-fibril-structure-bares-all

2. Gremer, Science, (2017). [Epub ahead of print]. DOI: 10.1126/science.aao2825  

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/28882996

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