Development of the Enzyme Immunoassay Systems for the Substances Involved in the Cause of Alzheimer's Disease

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Alzheimer's disease is a disease of unknown cause that is characterized by a progressive loss of memory and other cognitive functions, leading to a severe form of dementia and ultimately death. Neuropathologically, senile plaques and neurofibrillary tangles constitute the main features of Alzheimer's disease and it appears likely that they lead to the neuronal degeneration that characterizes the disease. One of the most consistent neuropathdlogical findings is the degeneration of magnocellular cholinergic nerve cells in the nucleus basalis of Meynert. Nerve growth factor (NGF) administration reduces the basal forebrain cholinergic neuron atrophy and the spatual memory impairment that are associated with normal aging in rats. Purpose of this research was thus to develop the highly sensitive enzyme immunoassay (EIA) systems for various neurotrophic factors involved in the cause of Alzhei mer's disease and to apply these developed EIA systems for the diagnosis of the Alzheimer's disease.M … More ajor results are summarized as follows; (1) We developed the purification procedures for many biologically active substances, which are concerned in the cause of the disease, including NGF, epidermal growth factor (EGF), superoxide dismutase (SOD), pletelet-derived growth factor (PDGF), etc. (2) By using the highly purified these substances, we prepared their monoclonal and polyclonal antibodies against rabbits of mice. (3) By using these antibodies prepared, we developed their highly sensitive, simple, and reliable two-site enzyme immunoassay systems. The minimum amounts of these substances detected by these enzyme immunoassay systems were approximately 10-15 pg/ml when a 100 pg aliquot of the sample was used. Good reproducibilities of within- and between-assay series and excellent recovery of exogenous substances from serum were observed. (4) We demonstrated that catecholamines increased the NGF content in medium conditioned by mouse L-M fibroblast cells and mouse astroglial cells. In this research, we demonstrated that catecholamines enhanced NGF synthesis of L-M cells and astroglial cells by increasing the cellular content of NGF MRNA and the affects of catecholamines were not mediated by adrenergic receptors. Coenzyme Q and vitamin K analogues also found to stimutate the NGF synthesis of astroglial cells. Less