Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects.

Background: Quantification of Amyloid beta (Aβ) oligomers in plasma enables early diagnosis of Alzheimer's Disease (AD) and improves our understanding of underlying pathologies. However, quantification necessitates an extremely sensitive and selective technology because of very low Aβ oligomer concentrations and possible interference from matrix components.

Methods: In this report, we developed and validated a surface-based fluorescence distribution analysis (sFIDA) assay for quantification of Aβ oligomers in plasma.

Accurate design of high-affinity protein binding macrocycles using deep learning.

The development of macrocyclic binders to therapeutic proteins typically relies on large-scale screening methods that are resource-intensive and provide little control over binding mode. Despite considerable progress in physics-based methods for peptide design and deep-learning methods for protein design, there are currently no robust approaches for design of protein-binding macrocycles. Here, we introduce RFpeptides, a denoising diffusion-based pipeline for designing macrocyclic peptide binders against protein targets of interest.

Exploring Arylidene-Indolinone Ligands of Autophagy Proteins LC3B and GABARAP.

We report the first structure-activity studies of arylidene-indolinone compound which was reported as a ligand of autophagy-related protein LC3B. The literature has conflicting information on the binding affinity of this compound and there is some debate regarding its use as a component of autophagy-dependent degrader compounds. We developed an AlphaScreen assay to measure competitive inhibition of the binding of known peptide ligands to LC3B and its paralog GABARAP.

Elevated Aβ aggregates in feces from Alzheimer's disease patients: a proof-of-concept study.

Background: Misfolding and aggregation of amyloid β (Aβ), along with neurofibrillary tangles consisting of aggregated Tau species, are pathological hallmarks of Alzheimer's disease (AD) onset and progression. In this study, we hypothesized the clearance of Aβ aggregates from the brain and body into the gut.

Methods: To investigate this, we used surface-based fluorescence intensity distribution analysis (sFIDA) to determine the Aβ aggregate concentrations in feces from 26 AD patients and 31 healthy controls (HC).

IAPP - oligomerisation levels in plasma of people with type 2 diabetes.

Islet amyloid polypeptide (IAPP) is co-secreted with insulin from pancreatic ß-cells. Its oligomerisation is regarded as disease driving force in type 2 diabetes (T2D) pathology. Up to now, IAPP oligomers have been detected in affected tissues.