Abstract

We will attempt to identify sensitive cholinergic markers in the CSF and to develop provocative neuropharmacological tests which will detect early Senile Demetia of Alzheimers Type (SDAT). By using the most sensitive techniques presently available, we will monitor the level of several parameters of acetylcholine (ACh) metabolism in the lumbar cerebrospinal fluid (CSF) of SDAT patients and controls. These assays will include ACh and choline (Ch) levels and choline acetyltransferase (ChAc) and acetyl cholinesterase (AChE) activities. The molecular forms (isozymes) of AchE will be separated and studied by isoelectric focusing and gradient microsedimentation analysis. The Ch/ACh, ChAc/ACh and AChE/ACh ratios in CSF will be detemrined. In a parallel study of the same patients, using acute i.v. administration, the effect of physostigmine and scopolamine on short-term memory function will be tested. Plasma and CSF levels of physostigmine will be monitored by means of a new HPLC method developed in our laboratory. Physostigmine levels, ACh and Ch levels, AChE and ChAc activities and effects on cognitive function will be correlated. This study will be the first to combine quantitative CSF analysis with pharmacological provocative tests and to simultaneously monitor physostigmine plasma levels in SDAT patients and healthy elderly controls.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG005416-03
Application #
3116072
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1985-12-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1989-11-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Southern Illinois University School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
Springfield
State
IL
Country
United States
Zip Code
62794

  Publications

Messamore, E; Warpman, U; Ogane, N et al. (1993) Cholinesterase inhibitor effects on extracellular acetylcholine in rat cortex. Neuropharmacology 32:745-50
Giacobini, E (1993) Pharmacotherapy of Alzheimer disease: new drugs and novel strategies. Prog Brain Res 98:447-54
Messamore, E; Warpman, U; Williams, E et al. (1993) Muscarinic receptors mediate attenuation of extracellular acetylcholine levels in rat cerebral cortex after cholinesterase inhibition. Neurosci Lett 158:205-8
Giacobini, E (1991) Nicotinic cholinergic receptors in human brain: effects of aging and Alzheimer. Adv Exp Med Biol 296:303-15
Manyam, B V; Giacobini, E; Colliver, J A (1990) Cerebrospinal fluid acetylcholinesterase and choline measurements in Huntington's disease. J Neurol 237:281-4
Pomponi, M; Giacobini, E; Brufani, M (1990) Present state and future development of the therapy of Alzheimer disease. Aging (Milano) 2:125-53
Manyam, B V; Giacobini, E; Ferraro, T N et al. (1990) Cerebrospinal fluid as a reflector of central cholinergic and amino acid neurotransmitter activity in cerebellar ataxia. Arch Neurol 47:1194-9
Giacobini, E (1990) Cholinergic receptors in human brain: effects of aging and Alzheimer disease. J Neurosci Res 27:548-60
Sugaya, K; Giacobini, E; Chiappinelli, V A (1990) Nicotinic acetylcholine receptor subtypes in human frontal cortex: changes in Alzheimer's disease. J Neurosci Res 27:349-59
Manyam, B V; Giacobini, E; Colliver, J A (1990) Cerebrospinal fluid choline levels are decreased in Parkinson's disease. Ann Neurol 27:683-5

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