Misfolding of Amyloid-beta and tau in Alzheimer’s and Other Neurodegenerative Diseases

Misfolding of Amyloid-beta and tau in Alzheimer?s and Other Neurodegenerative Diseases describes historical discoveries of these two major proteins in Alzheimer?s disease and other neurodegenerative conditions. The book navigates through the importance of protein self-assembly, protein conformational change, and structural studies in understanding the positioning in the disease pathway. How these proteins are involved in the pathway to neuronal dysfunction, and the importance of understanding protein conformation and deposition for diagnosis are also highlighted. Although Alzheimer?s disease was discovered over 100 years ago, the role of protein misfolding in the pathology and cause of Alzheimer?s disease remains unclear. Amyloid-beta and Tau are both proteins well known for their involvement in Alzheimer?s disease. Both proteins misfolding and aggregate are deposited as cross-beta amyloid fibrils in the tissues.

1. Historical perspective: introduction to the discovery of pathological proteins deposited in Alzheimer’s disease
2. Genetics of Alzheimer’s disease and the generation of Amyloid beta
3. Genetics of tauopathies
4. Self-assembly of Amyloid-beta and tau (Kinetics, conformational change, role of sequence, mutations)
5. Structure of amyloid fibrils formed by Amyloid-beta and tau: latest perspectives from CryoEM and what has led up to its contribution
6. The role of amyloid beta and tau in disease: how might oligomers and fibrils affect neuronal health and physiological health in humans
7. Therapeutics that target amyloid beta and tau generation and aggregation
8. Diagnostics: using the deposition and conformational status of Amyloid beta and tau for diagnosis (MRI; CSF analysis and Prion seeding assays)
9. Interaction: how do Amyloid beta and tau influence one another?
10. Other proteins: the contribution of ApoE genotype to amyloid and tau aggregation and clearance
11. Other proteins: The role of chaperone system in disease: proteostasis and disease
12. Future perspectives: what the future holds and where will research go next?

Professor Louise Serpell is a Professor of Biochemistry at the University of Sussex, UK and a Director of Sussex Neuroscience. Her work focusses on protein self-assembly and misfolding at the heart of neurodegenerative diseases and amyloidosis. Louise Serpell has been conducting research to understand neurodegenerative diseases for over 25 years. She did her PhD in Oxford in 1992-1995 and then spent as a postdoc 2 years in Toronto, Canada before returning to work in Cambridge where she set up an independent research group. She has been working at the University of Sussex for 18 years. She has an interest in protein self-assembly. A major aim of her research group is to understand the underlying causes of Alzheimer’s disease (AD). Her research group uses a highly multidisciplinary approach to investigate these questions incorporating a fibrous protein structure determination and neuroscience to examine the protein related mechanisms that lead to AD.