The goal of this project is to determine whether deficits in cytosolic free calcium are diagnostic for Alzheimer's disease. Several deficits in calcium homeostasis and calcium dependent processes have been described for peripheral tissues from Alzheimer's patients; these include a deficits in calcium homeostasis, a decline in protein phosphorylation, growth factor response, cell spreading, glucose and glutamine oxidation. The main objective of this proposal is to determine whether the deficits in cytosolic free calcium concentration in cultured skin fibroblasts from Alzheimer's patients differ from that in patients with other dementing illnesses (e.g., Pick's disease, Parkinson's dementia, multi-infarct dementia). The mechanisms for the decline in cytosolic free calcium in Alzheimer's disease are unclear. The calcium binding proteins play a role in buffering intracellular calcium and studies are designed to determine whether they are altered during Alzheimer's disease. Fibroblasts from individuals who are at risk for developing Alzheimer's disease (e.g. familial Alzheimer's disease) will also be tested to determine whether deficits in cytosolic free calcium appear prior to the clinical signs of the disorder. These approaches will help us to diagnose Alzheimer's disease, understand the mechanisms that underlie the degenerative disorder and aid in the design of effective therapeutic strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AG007855-02
Application #
3453237
Study Section
Neurology A Study Section (NEUA)
Project Start
1988-07-01
Project End
1993-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Peterson, C (1992) Changes in calcium's role as a messenger during aging in neuronal and nonneuronal cells. Ann N Y Acad Sci 663:279-93
Peterson, C; Vanderklish, P; Seubert, P et al. (1991) Increased spectrin proteolysis in fibroblasts from aged and Alzheimer donors. Neurosci Lett 121:239-43
Peterson, C; Giguere, J F; Cotman, C W et al. (1990) Selective loss of N-methyl-D-aspartate-sensitive L-[3H]glutamate binding sites in rat brain following portacaval anastomosis. J Neurochem 55:386-90
Peterson, C; Cotman, C W (1990) Decreased survival of hippocampal neurons in medium conditioned by fibroblasts from aged and Alzheimer donors. Brain Res 515:39-44
Peterson, C (1990) Tetrahydroaminoacridine increases acetylcholine synthesis and glucose oxidation by mouse brain slices in vitro. Neurosci Lett 115:274-8
Seubert, P; Peterson, C; Vanderklish, P et al. (1990) Increased spectrin proteolysis in the brindled mouse brain. Neurosci Lett 108:303-8
Peterson, C; Cotman, C W (1989) Strain-dependent decrease in glutamate binding to the N-methyl-D-aspartic acid receptor during aging. Neurosci Lett 104:309-13
Peterson, C; Neal, J H; Cotman, C W (1989) Development of N-methyl-D-aspartate excitotoxicity in cultured hippocampal neurons. Brain Res Dev Brain Res 48:187-95
Peterson, C; Ratan, R; Shelanski, M et al. (1989) Changes in calcium homeostasis during aging and Alzheimer's disease. Ann N Y Acad Sci 568:262-70