Binghamton University Research Challenges Alzheimer's Core Theory
More than 7 million Americans over 65 live with Alzheimer's. For years, the prevailing scientific belief has been that the disease originates from amino acid fragments aggregating in the brain, leading to plaque formation, degradation, and neuron death.
Recent studies, including research at Binghamton University, are beginning to challenge this central hypothesis.
Unraveling Amyloid-Beta's Initiation
Chemistry Professor Wei Qiang at Binghamton University has been investigating Amyloid-beta peptides, which are believed to initiate Alzheimer's. His research focuses on understanding how these individual fragments assemble into structures and how they interact with lipids, causing membrane disordering.
This inquiry aims to determine which parts assemble first and interact with lipids during the process.
Advanced Techniques for Disordered Systems
Professor Qiang utilizes solid-state nuclear magnetic resonance (NMR) spectroscopy, a technique particularly suitable for studying disordered systems. This method allows him to capture snapshots of amyloid aggregation at various stages.
Initially, his research involved artificially synthesized membrane models in the lab, but it has now progressed to real cell systems.
Overcoming Experimental Hurdles
Working with living cells presents challenges, as they are difficult to keep alive. Experiments are conducted at the National Magnetic Lab in Florida, where cryogenic-level temperatures allow for significantly enhanced NMR sensitivity.
The long-term objective is to advance from undifferentiated cell lines to conducting experiments on full, real neurons.
Paving the Way for New Therapies
The fundamental studies conducted by Qiang's team aim to provide information crucial for designing agents that could prevent the aggregation process. This information is analogous to structural data used by pharmaceutical companies for drug design, even though the early-stage, disordered nature of the amyloid system presents unique challenges in identifying specific protein structures or binding pockets.
The Puzzle of Structural Polymorphism
In addition to studying aggregation, Qiang's research seeks to understand how amyloid structures, known as fibrils, proliferate in the brain. He is investigating the significance of structural polymorphism, where fragmented peptides can adopt multiple structures.
This aspect questions the linear cascade hypothesis for Alzheimer's development, especially given past failures in drug designs that targeted specific Amyloid-beta aggregate structures.
Qiang's work suggests that understanding the diversity of structures within the system is critical for developing more effective treatments.
Funding Innovation
Professor Qiang's research has received approximately $2 million from the NIH's National Institute for General Medical Sciences since 2018, with additional funding from the S.H. Ho Research Foundation.