Field of the invention: The present invention relates to reagents and methods for drug screening and, more particularly, neuronal cells and tissue for screening potential Alzheimer therapeutics. Background: In 1907, Alois Alzheimer described the case of a 51-year-old...
Field of the invention: The present invention relates to reagents and methods for drug screening and, more particularly, neuronal cells and tissue for screening potential Alzheimer therapeutics. Background: In 1907, Alois Alzheimer described the case of a 51-year-old woman with a rapidly degenerating memory who (after a swift deterioration) died severely demented four years later. This condition, which now bears Alzheimer's name, describes a fatal degenerative dementing disorder with initial mild memory impairment that progresses unrelentingly to a total debilitating loss of mental and physical faculties. Following symptom onset, the course of the disease varies considerably from a few years to over 20 years, with a mean survival of approximately 8 years. M. A. Smith, "Alzheimer Disease," Internat. Rev. Neurobiol. 42:1 (1998). Alzheimer disease affects 10-15% of individuals over 65 years and up to 47% of individuals over the age of 80. In both clinical and autopsy series in the United States and Europe, Alzheimer disease accounts for approximately two-thirds of all dementias affecting elderly individuals. D. A. Evans et al., J. Am. Med. Assoc. 262: 2551 (1989).The most common and distinctive lesions present with the diseased brain are the neuritic senile plaques and neurofibrillary tangles. The major protein component of senile plaque cores and vascular amyloid is a small polypeptide of approximately 4.2 kDa termed amyloid-.beta.. A significant fraction of this protein is found to be associated with the cytoskeleton, presumably through its interaction with the microtubule-associated .tau. ("tau") protein. It is believed that the increased phosphorylated status of tau protein represents one of the earliest neuronal changes prior to the development of neurofibrillary tangles. Unfortunately, because of the heterogeneity of the factors thought to be responsible for Alzheimer disease and the lack of an animal model displaying the full spectrum of pathological changes, successful pharmacological interventions have not been established. What is needed is an easy, reliable method to determine the safety and efficacy of candidate therapeutics for the treatment and/or prevention of Alzheimer disease. Definitions: The term "drug" as used herein, refers to any medicinal substance used in humans or other animals. Encompassed within this definition are compound analogs, naturally occurring, synthetic and recombinant pharmaceuticals, hormones, neurotransmitters, etc. The present invention contemplates screening test compounds to identify a useful drug for the treatment of Alzheimers. Most current attempts at therapeutics for Alzheimer disease are directed at neurotransmitter deficiencies. The term "neurotransmitter" includes any compound which functions in the nervous system to result in the transmission of chemical signals between cells.