The role of Aβ degrading enzymes in Alzheimer's disease
Dr Kehoe's interest in the RAS pathway is not only on its distribution in the brain but also its behaviour with respect to Alzheimer's disease. In relation to this he is spear-heading a programme grant with Dr Scott Miners and Professor Seth Love where ACE activity and levels are being examined along with a number of other Aβ degrading enzyme candidates are being examined in brain homogenates and cerebrospinal fluid of Alzheimer's patients and non-demented elderly and the correlations of these data with variables already collected of Alzheimer's disease pathology and genetic variation. This area of Aβ degrading enzyme work also includes additional projects which are: a Reverend Williams funded graduate student (Jen Palmer) project investigating the role of both endothelin converting enzymes in Alzheimer's disease; a BRACE funded graduate student (Rachel Barker) on the role of plasmin in pathology of Alzheimer's disease and a James Tudor Foundation grant, spear-headed by Professor Seth Love with Dr Shabnam Baig, Dr Kehoe and Dr Scott Miners to examine the potential of measuring neprilysin as a biomarker for the diagnosis of Alzheimer's disease. For further detail on all of these projects please see visit the link entitled the role of altered expression of Aβ degradative enzymes in the pathogenesis of AD and CAA on our research interests page.
Finally Dr Kehoe is increasingly interested in the investigation of the role of anti-hypertensive medications in Alzheimer's disease and whether they promote cognitive improvement and/or whether they may have deleterious effects on Alzheimer's disease pathology. In his pursuit of this work he is collaborating with members of the European Alzheimer's Disease Consortium (EADC) on which he is an Executive Committee Member to investigate the impact of ACE-inhibitor use on rates of cognitive decline in people with Mild Cognitive Impairment that have been collected as part of DESCRIPA (Development of Screening guidelines and diagnostic Criteria for Predementia Alzheimer's disease). He is also the principal investigator on a new recently ART funded study which, in collaboration with colleagues at the University of Edinburgh, will compare the potential impact of ACE-inhibitors with Angiotensin Receptor Blockers or placebo on Alzheimer's disease like pathology.