Biochemical Genetics Group: The Laboratory continue to use the forward genetics approach to search for quantitative and/or qualitative disease- associated changes in gene products (proteins) in tissues and body fluids. The Laboratory used this approach in the past to find a CSF protein that was elevated in Creutfeldt-Jacob diseases and in 1/3 of patients with schizophrenia. As this protein is a trace protein which is found at the tenth of a nanogram level in our electrophoretograms, purification and sequencing has been difficult and time consuming. Recently we identified a 20 kDa protein in cerebrospinal fluid which is increased two-fold or more in most individuals with Alzheimer's disease. Through collaborative efforts with Dr. William Wallace at Mt. Sinai, the Laboratory has been examining protein variations in the brains from patients who died from Alzheimer's disease. The Laboratory has also initiated the exploration of animal models for this disease. These studies have demonstrated an increased biosynthesis of the Alzheimer's amyloid precursor protein in the cerebral cortex of rats with lesions of the nucleus basalis of Meynert. In addition, we have found that there is increased synthesis and accumulation of heat shock 70 proteins and an increase in the phosphorylation of elongation factor two, a protein which is essential in protein synthesis, in postmortem tissue from patients with Alzheimer's disease.