Extracellular matrix, cell-surface receptors and Alzheimer's disease: a novel glycoform of acetylcholinesterase

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Alzheimer's disease is the leading cause of dementia in the elderly, affecting approximately 5-10% of the population over the age of 65. With an increasingly ageing population, Alzheimer's disease will be a major health problem in the next century unless effective treatments (probably in combination with early diagnosis) are found. We have identified a novel form of a protein acetylcholinesterase (AChE-AD), which is present in high levels in the brains of patients with Alzheimer's disease. Our work has shown that the accumulation of another protein in the brains of Alzheimer patients, known as the amyloid protein, is the cause of the increase in AChE-AD. This finding is important for two reasons: 1) Identification of the mechanism by which the amyloid protein causes an increase in AChE-AD will tell us about some of the basic causes of Alzheimer's disease. 2) AChE-AD may be a useful diagnostic marker of Alzheimer's disease. At present, diagnosis is performed by clinical examination. This is a time consuming and inaccurate process. A biochemical diagnostic marker will provide an objective criterion with which to diagnose Alzheimer's disease. Therefore, our research is aimed at: Aim 1: Evaluating AChE-AD as a diagnostic marker. Aim 2: Developing tools with which we can more easily measure AChE-AD. Aim 3: Understanding the basic biochemical mechanisms which cause the increase in AChE-AD in the brains of patients. Aim 4: Examining whether AChE-AD may contribute to the cause of Alzheimer's disease.