Neurobiology of Alzheimer's Disease

David Dawbarn obtained his PhD from the University of Bristol and then initiated his work on Alzheimer's disease (AD) at the Medical Research laboratories in Cambridge as a Research Fellow. He returned to Bristol to take up a lectureship investigating the molecular pathology of Alzheimer's disease and developing new therapies. His interests are in nerve growth factor (NGF) and Alzheimer's disease; his early work described the distribution of NGF receptors in the brain, showing their specific localisation on cholinergic neurons. The identity of the NGF binding site on its receptor was then determined. The domain was made as a recombinant protein, crystallised and its structure solved. The coordinates of the structure are currently being used for the development of small molecule therapeutics for the treatment of Alzheimer's disease.Shelley Allen obtained her PhD at the Institute of Neurology in London, and her work in the early eighties with David Bowen started her interest in the cholinergic changes in Alzheimer brain. Later at Bristol she investigated the characterisation of human cholinergic basal nucleus in terms of the nerve growth factor (NGF) receptor. She has continued this work on the neurotrophins and the possibility of a neurotrophin related therapeutic for Alzheimer's disease. In addition she is especially interested in the influence of cholinergic activity on Alzheimer-associated pathogenic processes. Her work recently has also shown variously the synaptic loss associated with the E4 allele of apolipoprotein E in normal individuals and the increase in BACE activity in sporadic Alzheimer's disease.

essential reading...accessible and useful to...students, researchers, clinicians and pharmacists

• 1. Alzheimer's disease: a hundred years of investigation ; 2. The neuropathology of Alzheimer's disease ; 3. Molecular genetics of Alzheimer's disease ; 4. Biology and molecular neuropathology of beta-amyloid protein ; 5. The molecular basis of tau protein pathology: role of abnormal hyperphosphorylation ; 6. Protein misfolding, aggregation and fibril formation: common features of cerebral and non-cerebral amyloidosis ; 7. Apolipoprotein E, amyloid beta-peptide and Alzheimer's disease ; 8. Presenilins ; 9. Multiple transgenic mouse models for Alzheimer's disease ; 10. Inflammation and Alzheimer's disease ; 11. Cellular targets of amyloid beta-peptide: potential roles in neuronal cell stress and toxicity ; 12. Alzheimer's disease as a neurotransmitter disease ; 13. NGF family of neurotrophins and their receptors: early involvement in the progression of Alzheimer's disease ; 14. Clinical assessment of Alzheimer's disease ; 15. Molecular and biological markers for Alzheimer's disease ; 16. Current pharmacological approaches to treating Alzheimer's disease ; 17. Amyloid-based therapies ; 18. Future directions: the A-beta amyloid pathway as the target for diagnosing, preventing or treating Alzheimer's disease