Imagine if amyloid-β (Aβ) were a pesky weed growing in the garden of your brain, causing trouble and increasing the risk of Alzheimer’s disease (AD). Well, scientists have discovered a new player in the fight against this troublesome weed – A Disintegrin and Metalloproteinase with Thrombospondin motifs 1 (ADAMTS1)! And how does ADAMTS1 work? It acts like a special tool that can help inhibit the growth of Aβ by reducing its production. Just as gardening enthusiasts would want to prevent weeds from spreading, researchers found that ADAMTS1 can decrease Aβ generation by inhibiting a specific enzyme called β-secretase. This exciting study also found that ADAMTS1 can reduce the burden of Aβ in the hippocampus, a brain region critical for memory and learning. By introducing ADAMTS1, the cognitive abilities of mice models with AD-like symptoms improved. These findings suggest that ADAMTS1 may be an important link between genetics and lifestyle factors that influence AD risk. If you’re interested in learning more about this groundbreaking research and how ADAMTS1 could potentially mitigate the risk of Alzheimer’s disease, be sure to check out the full study!
Amyloid-β (Aβ) derived from amyloid precursor protein (APP) hydrolysis is acknowledged as the predominant hallmark of Alzheimer’s disease (AD) that especially correlates to genetics and daily activities. In 2019, meta-analysis of AD has discovered five new risk loci among which A Disintegrin and Metalloproteinase with Thrombospondin motifs 1 (ADAMTS1) has been further suggested in 2021 and 2022. To verify the association, we re-sequenced ADAMTS1 of clinical AD samples and subsequently identified a novel rare variant c.–2067A > C with watchable relevance (whereas the P-value was not significant after adjustment). Dual-luciferase assay showed that the variant sharply stimulated ADAMTS1 expression. In addition, ADAMTS1 was also clearly induced by pentylenetetrazol-ignited neuronal activity and enriched environment (EE). Inspired by the above findings, we investigated ADAMTS1’s role in APP metabolism in vitro and in vivo. Results showed that ADAMTS1 participated in APP hydrolysis and consequently decreased Aβ generation through inhibiting β-secretase-mediated cleavage. In addition, we also verified that the hippocampal amyloid load of AD mouse model was alleviated by the introduction of ADAMTS1, and thus spatial cognition was restored as well. This study revealed the contribution of ADAMTS1 to the connection of genetic and acquired factors with APP metabolism, and its potential in reducing hippocampal amyloid and consequent risk of AD.
Dr. David Lowemann, M.Sc, Ph.D., is a co-founder of the Institute for the Future of Human Potential, where he leads the charge in pioneering Self-Enhancement Science for the Success of Society. With a keen interest in exploring the untapped potential of the human mind, Dr. Lowemann has dedicated his career to pushing the boundaries of human capabilities and understanding.
Armed with a Master of Science degree and a Ph.D. in his field, Dr. Lowemann has consistently been at the forefront of research and innovation, delving into ways to optimize human performance, cognition, and overall well-being. His work at the Institute revolves around a profound commitment to harnessing cutting-edge science and technology to help individuals lead more fulfilling and intelligent lives.
Dr. Lowemann’s influence extends to the educational platform BetterSmarter.me, where he shares his insights, findings, and personal development strategies with a broader audience. His ongoing mission is shaping the way we perceive and leverage the vast capacities of the human mind, offering invaluable contributions to society’s overall success and collective well-being.