Alzheimer’s disease (AD) is an increasingly serious problem in all societies with ageing populations. In the UK the Alzheimer Disease Society estimates its current incidence as approaching 800,000, likely to increase to up to 1.2 million over the coming decade. The disease, characterized by neurodegeneration, is progressive. Thus the discovery of an effective agent to alleviate the cognitive and memory deficits characteristic of the early stages of the disease is a high priority, even if neurodegeneration itself can only be slowed rather than halted. The recognition that many if not all the cascade of biochemical events characteristic of AD which lead to cell death and plaque accumulation are triggered by the improper processing of the amyloid precursor protein, APP (the so-called amyloid hypothesis) has led to increased attention being paid to the possible role of APP in memory-related processes and to its malfunction as helping explain the memory deficits in the disease. Therefore, our research effort is focused on peptides derived from the amyloid precursor protein as starting points for the development of a therapeutic agent to ameliorate the cognitive decline in Alzheimer’s disease to the point of entry to the clinic. Our model system is one-day old chick. The advantages of this model system are: chick APP is 95% identical to human APP over its entire length, whilst the amyloid beta sequence is 100% identical; the distribution of APP isoforms in the chick is, as in humans, ubiquitous; the chick expresses the all the genes for the main proteolytic proteases implicated in the non-amyloidogenic and the amyloidogenic processing of APP; the degree of APP gene expression is related to the strength of memory retention (http://intranet.open.ac.uk/personalpages/r.mileusnic/index.htm; http://www.stevenroseonline.net/SPRR/Welcome.html). Collaboration with Professor Peter K. Giese (http://www.iop.kcl.ac.uk/staff/profile/default.aspx?go=11361) extended this research to mammalian systems.
