New Publication – OpenSPR™ Binding Data Reveals Novel Mechanisms of Alzheimer’s Disease

Over 50 million people worldwide have been diagnosed with Alzheimer’s Disease (AD) or another form of dementia, according to the World Alzheimer Report 2018 (Patterson, 2018). This totals an estimated $1 Trillion USD in cost of care. It is no surprise that AD is a significant area of research today as scientists hope to find an effective therapeutic strategy for this debilitating disease.

Currently, researchers are attempting to exploit the fact that D-amino acid substitution has been observed in many neurodegenerative disease-related peptides and proteins (Li, Delaney, Li, 2019). Particularly, the chiral inversion of the amino acid amyloid beta (Aβ) is believed to play a significant role in the pathological development of AD (Li, et al., 2019). Unfortunately, distinguishing the subtle chiral differences induced by D-amino acid substitution is not trivial. This has made the mechanisms underlying chiral chemistry in disease progression and therapeutic treatment poorly understood.

Fortunately, Lingjun Li and the rest of her team are working on a novel methodology to better understand how chirality is affecting the self-assembly/oligomerization as well as receptor recognition of Aβ fragments. Based primarily upon mass spectroscopy measurements, Li introduces her novel method known as iCAP in her recent publication in Nature Communications, “Molecular basis for chirality-regulated Aβ self-assembly and receptor recognition revealed by ion mobility-mass spectrometry. Our team at Nicoya is so excited to see the OpenSPR™  play a significant role in iCAP by providing quantitative binding kinetics data. In this blog, we summarize how iCAP studies the effects of chirality and how surface plasmon resonance provides crucial binding kinetics data to study the effects of chirality on Aβ receptor recognition.

iCAP in Three Steps

Step 1: Discriminating chiral Aβ fragment monomers

The first step of iCAP deals directly with amyloid beta (Aβ) monomers. The goal here is to distinguish between D and L epimeric monomers since there is a particular interest in studying the D epimers. Using travelling wave ion-mobility separation–mass spectrometry (TWIMS-MS), the structural differences between the two epimers are amplified by metal coordination and then visualized using 3D scattering collisional cross-section (CCS) values. Due to the difference in each epimer’s ability to coordinate with metals, the D and L epimers show diverse binding ratios and their complexes show significant structural differences. This allowed the Li group to study Aβ fragment monomers of a particular chirality.

Step 2: Discriminating chiral Aβ fragment oligomers

Li et al. (2019) write that “One of the AD hallmarks is extracellular amyloid plaque deposition in the brain, which is believed to be linked to the Aβ self-assembly/oligomerization” (p. 4). In other words, studying the way different Aβ epimers oligomerize will provide significant insight into their mechanism contributing to Alzheimer’s Disease. In the next step of iCAP, Aβ self-assembly/oligomerization is studied using the same chiral amplification method used in the first step. The growth curves of the oligomers are plotted by analyzing their measured CCS values against their oligomeric number.

Since the wild-type (aka L epimer) of Aβ and the D-isomerized version often coexist, the Li group was particularly interested in studying a mixture of several forms of Aβ peptides to study their cross-talking chiral effects. In doing this, the Li group noticed that the chiral effects of D-isomerized Aβ fragments on self-assembly/oligomerization were even greater as a mixture than on its own. Since Aβ will occur naturally as a mixture, this is significant evidence that D-isomerized Aβ fragments could be contributing to the progression of AD.

Step 3: Studying chiral Aβ-receptor recognition using surface plasmon resonance

As the last step in iCAP, it was crucial for the Li group to study how the chirality of Aβ affects the way it interacts with one of its natural receptors – tetrameric transthyretin (TTR). Using their OpenSPR™ instrument, TTR was immobilized to a carboxyl sensor chip. Different fragments of wild-type and D-isomerized Aβ were then injected in PBS buffer at various concentrations. Each binding experiment was performed three times with biologically independent samples to obtain the average on rate (Kon), off rate (Koff), and overall binding affinity (KD) of each Aβ fragment with TTR.

Upon analyzing the kinetic results from their SPR kinetics, the Li group found that D-isomerized co-isomerized Aβ fragments had binding affinities 8-10 times lower than wild-type Aβ, and dissociation rates that were 13-15 times higher. In other words, D-isomerized Aβ fragments significantly lower Aβ’s ability to bind its natural receptors. Collision induced unfolding (CIU) was also used as a gas-phase technique to obtain structural data about these interactions.

Get the data you need to publish with OpenSPR™

Thanks to the development of iCAP, the Li group was able to provide a comprehensive evaluation of how chirality is affecting the self-assembly/oligomerization as well as receptor recognition of Aβ fragments. Through the extensive amount of data obtained from this platform, iCAP could one day help facilitate the design of novel therapeutic treatments for Alzheimer’s Disease that specifically target D-isomerized and co-isomerized Aβ fragments. This technique could theoretically be used to investigate similar chiral systems as well.

With quantitative binding kinetics playing a key role in the effectiveness of iCAP, the Li group chose the OpenSPR™ to get them the data they need. At Nicoya, we help scientists succeed by providing affordable and easy-to-use surface plasmon resonance instrumentation. Lingjun Li is one of the many researchers who are using OpenSPR binding data to publish in high-impact journals like Nature Communications.

Publish your research with affordable SPR instrumentation.



  1. Patterson, C. (2018). World Alzheimer Report 2018. Retrieved from Alzheimer’s Disease International: Li, G.,
  2. DeLaney, K., Li, L. (2019). Molecular basis for chirality-regulated Aβ self-assembly and receptor recognition revealed by ion mobility-mass spectrometry. Nat Commun, 10(5038), 1-11. doi:10.1038/s41467-019-12346-8