Neurochemistry of Alzheimer’s disease
Alzheimer’s disease (AD) and other dementias affect over 750,000 people in the UK and the annual cost of care is estimated at £23 billion. AD is characterised by regionally selective gross cerebral atrophy (Figure 1), senile plaques, neurofibrillary tangles together with selective neurone and synapse loss. The principal neuronal types affected used glutamate or acetylcholine as transmitter. These changes produce a characteristic clinical syndrome of progressive cognitive dysfunction and behavioural abnormalities with declining activities of daily living. Current treatments are based reducing the breakdown of acetylcholine in the synaptic cleft and they provide symptomatic benefit for a majority of patients. Other forms of dementia include Vascular dementia, Frontotemporal dementia and Lewy body dementia.
The research of this group focuses on the relationship between neurochemical changes in the brains of patients with dementia and their particular symptoms. Thus we have shown that, in addition to the well-known relationship between acetylcholine and cognitive decline (Figure 2), there is a relationship between this system and non-cognitive, behavioural changes seen in patients with AD. This then provides a scientific rationale for the clinical improvement in this domain following treatment with acetylcholinesterase inhibitors (AChEI).
We are also interested in the mechanism of action of AChEIs and a newly approved drug in the AD field, memantine. We have argued that AChEIs work by increasing the release of glutamate (Figure 3) that is reduced in AD as a consequence of glutamatergic cell and synapse loss. Memantine has been shown to be clinically useful in people with dementia who exhibit aggressive symptoms and our studies show that this benefit is likely to flow from actions of the drug on the phosphorylation status of tau protein.
Gross cerebral atrophy in a brain from a patient with Alheimer's disease
Ach synthesis and dementia in living AD patients
Treatment with an anticholinesterase inhibitor increases glutamate release
Brains for Dementia Research is directed by Professor Francis and was established in 2007 to promote brain donation and establish a network of brain banks to facilitate research into dementia.
Brains for Dementia Research is funded by a £2.3M grant from the Alzheimer’s Society and the Alzheimer’s Research Trust. The Coordinating Centre is at WCARD and we have brain banks in London, Newcastle, Oxford, Manchester and Bristol. We are able to assist with the provision of human tissue for studies in dementia. To contact the office please send an email to email@example.com or telephone 020 7848 8377.
- Dr David Howlett/Honorary Senior Research Fellow
- Dr Julie Vallortigara/Postdoc(with Prof Ballard)
- Dr Martin Broadstock/Safra Research Fellow (with Prof Ballard)
- Dr Gillian Hayes/Senior Manager BDR
- Mr Richard Hudspith/BDR Manager
- Dr Nicholas Clarke/Consultant Psychiatrist & honorary research fellow
- Dr Mitchell Lai/Visiting Senior Research Fellow- Asst Prof National University of Singapore
- Ms Sindhoo Rangarajan/Technician