Dementia Research Group News
Dementia Research Group awarded £134,336 by BRACE
[Posted on 01 December 2006]
BRACE (Bristol Research into Alzheimer’s and Care of the Elderly) has awarded Dr Patrick Kehoe, Dr Scott Miners and Professor Seth Love, in the Dementia Research Group a further £134,336 in support of two PhD studentships, to examine the roles of ECE and plasmin in the development of Alzheimer’s disease. Dr Kehoe said “This funding will allow us to move rapidly to capitalize on our exciting novel observations and recent experimental data. The findings will have important clinical implications for the prediction of risk and improvement of diagnosis of Alzheimer’s disease and for its treatment and prevention.”Alzheimer’s disease is caused by the accumulation within the brain of a substance known as amyloid beta peptide (Aβ). Aβ is damaging to brain cells and in Alzheimer’s disease it accumulates in the brain to form plaques within the tissue, as well as large deposits in the walls of blood vessels. In most patients with Alzheimer’s disease, Aβ seems to be produced in normal amounts but accumulates because of defects in its removal. Recent studies in animal and isolated cells suggest that three enzymes neprilysin, endothelin converting enzyme (ECE) and plasmin are particularly important in the degradation and removal of Aβ. However, the applicability of these findings to the human brain and to Alzheimer’s disease has yet to be determined. With the support of charitable funds BRACE and the James Tudor Foundation, the Dementia Research Group has been investigating one of these candidates, neprilysin. The Group recently reported that the amount and activity of neprilysin within the brain are reduced in Alzheimer’s disease: the amount of neprilysin is reduced in nerve cells, blood vessels and in the (cerebrospinal) fluid that surrounds the brain. These reductions appear to be most marked in the patients who have the largest amounts of Aβ in their blood vessel walls.
These observations in relation to neprilysin raise several new and important questions, the answers to which should greatly improve understanding of how Alzheimer’s disease occurs and may help in the diagnosis of Alzheimer’s disease and, in time, in its prevention and treatment. These questions include whether or not the reduction in Aβ-degrading enyzme activity in Alzheimer’s disease is confined to neprilysin or also involves the other Aβ-degrading enyzmes (ECE and plasmin, in particular); whether reduction in Aβ-degrading enyzme activity might precede (and even cause) the clinical disease; and whether reduction in Aβ-degrading activity is related to genetic factors or to external influences such as diet.