Cerebrospinal Fluid Markers Of Aging And Brain Disease

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(1) Alzheimer disease (AD) is associated with accumulation of hyperphosphorylated tau protein within paired helical filaments of brain neurons. An immunologic ELISA assay was developed to measure the cerebrospinal fluid (CSF) concentration of tau protein phosphorylated at threonine 231. AD could be accurately diagnosed and its course followed with high specificity and selectivity by measuring phosphorylated tau in CSF. (2) Cultured PC12 cells were exposed to 0.1-100 micromole aluminum chloride for 6 hours. Northern blot analyses showed that the mRNA level of a subunit of cytochrome c oxidase, an enzyme in the mitochondrial electron transport chain, was reduced by 70% after exposure to only 1 micromole aluminum. This low concentration is found in postmortem brain from patients with AD and dialysis dementia, suggesting a toxic role for aluminum in these disorders. (3) Osmotic opening of the blood-brain barrier by intracarotid infusion of a hypertonic sugar solution is used clinically to treat malignant brain tumors and to grant access to brain of drugs and proteins in animal models. Opening involves the widening of tight junctions between vascular endothelial cells. Opening is mediated by increased intracellular Ca2+ and contraction of the endothelial cytoskeleton. Opening is prolonged in rats pretreated with a Na+/Ca2+ exchange blocker.