Understanding the Origins of Dementia using Antibodies

We are based at the Department of Chemistry at Imperial College London. Our research focuses on the development of biomolecules as research tools to understand disease mechanisms, and for clinical applications.
We use innovative high-throughput discovery methods to generate antibodies and peptides to study how the complex environment of the nervous system chemically modifies and modulates protein aggregates, called amyloids, which are a hallmark of many forms of dementia.

Antibody
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Antibody discovery

PNAS (2020) 117 (24), 13509-13518.

The accurate quantification of the amounts of small oligomeric assemblies formed by the amyloid β (Aβ) peptide represents a major challenge in the Alzheimer’s field. There is therefore great interest in the development of methods to specifically detect these oligomers by distinguishing them from larger aggregates. The availability of these methods will enable the development of effective diagnostic and therapeutic interventions for this and other diseases related to protein misfolding and aggregation. We describe here a single-domain antibody able to selectively quantify oligomers of the Aβ peptide in isolation and in complex protein mixtures from animal models of disease.

Protein Aggregation and Detection

Int. J. Mol. Sci. (2021) 22(8), 4128

Neurodegenerative disorders are a highly prevalent class of diseases, whose pathological mechanisms start before the appearance of any clear symptoms. This fact has prompted scientists to search for biomarkers that could aid early treatment. These currently incurable pathologies share the presence of aberrant aggregates called amyloids in the nervous system, which are composed of specific proteins. In this review, we discuss how these proteins, their conformations and modifications could be exploited as biomarkers for diagnostic purposes. We focus on proteins that are associated with the most prevalent neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, and frontotemporal dementia. We also describe current challenges in detection, the most recent techniques with diagnostic potentials and possible future developments in diagnosis.