Green, Alison J. E.; (1999) Brain-specific proteins in the diagnosis of dementia. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

With the mean age of the population increasing, the number of patients with dementia is likely to increase. Although Alzheimer's disease is the most common form of dementia, it is recognised that other forms of dementia are more prevalent than initially thought. As drug therapies become available, it will become important to obtain an accurate clinical diagnosis. Creutzfeldt-Jakob disease (CJD) is a rare type of dementia but with the emergence of the new variant form of this disease which affects young patients, and is thought to be related to the ingestion of meat or meat products from cattle affected with bovine spongiform encephalopathy (BSE), it is possible that it may become more common. These concerns have led to the search for diagnostic tests which may help in the early diagnosis of these forms of dementia. This study investigated whether measurement of cerebrospinal fluid (CSF) brain- specific proteins could be used in the assessment of patients with dementia. Four proteins were investigated: S-100b, an astrocytic protein; and three neuronal proteins, neurone-specific enolase, tau protein and 14-3-3. A two site sandwich ELISA was developed and evaluated for the measurement of S-100b. Levels of all four brain-specific proteins were raised in the majority of patients with sporadic CJD. The presence of CSF 14-3-3 had the best combination of sensitivity and specificity for detecting sporadic CJD. CSF 14-3-3 has recently been included in the diagnostic criteria for probable sporadic CJD. The value of measurement of these proteins in the new variant, iatrogenic and familial forms of CJD was also investigated. None of the CSF brain-specific proteins investigated was of value in the diagnosis of Alzheimer's disease.

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