(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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000139-03
Application #
6667885
Study Section
(BPMS)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Rapoport, Stanley I; Schapiro, Mark B; May, Conrad (2004) Reduced brain delivery of homovanillic acid to cerebrospinal fluid during human aging. Arch Neurol 61:1721-4
Buerger, Katharina; Zinkowski, Raymond; Teipel, Stefan J et al. (2003) Differentiation of geriatric major depression from Alzheimer's disease with CSF tau protein phosphorylated at threonine 231. Am J Psychiatry 160:376-9
Tendi, Elisabetta A; Bosetti, Francesca; Dasgupta, S Fenella et al. (2002) Ginkgo biloba extracts EGb 761 and bilobalide increase NADH dehydrogenase mRNA level and mitochondrial respiratory control ratio in PC12 cells. Neurochem Res 27:319-23
Buerger, Katharina; Zinkowski, Raymond; Teipel, Stefan J et al. (2002) Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231. Arch Neurol 59:1267-72
Bosetti, Francesca; Brizzi, Francesca; Barogi, Silvia et al. (2002) Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease. Neurobiol Aging 23:371-6
DasGupta, S F; Rapoport, S I; Gerschenson, M et al. (2001) ATP synthesis is coupled to rat liver mitochondrial RNA synthesis. Mol Cell Biochem 221:3-10
Bosetti, F; Solaini, G; Tendi, E A et al. (2001) Mitochondrial cytochrome c oxidase subunit III is selectively down-regulated by aluminum exposure in PC12S cells. Neuroreport 12:721-4
Hampel, H; Buerger, K; Kohnken, R et al. (2001) Tracking of Alzheimer's disease progression with cerebrospinal fluid tau protein phosphorylated at threonine 231. Ann Neurol 49:545-6
Rapoport, S I (2001) Advances in osmotic opening of the blood-brain barrier to enhance CNS chemotherapy. Expert Opin Investig Drugs 10:1809-18