Abstract

The in vivo functional activity of central nervous system (CNS) noradrenergic, vasopressinergic and cholinergic systems will be evaluated in vivo in patients with Alzheimer's disease (AD) and in comparison groups of patient's with multiinfarct dementia and both elderly and young normal subjects. These neuronal and endocrine systems appear abnormal in AD and affect behaviors impaired in AD. Three major questions will be addressed: 1) Is there decreased alpha-2 mediated suppression of CNS noradrenergic systems in AD? This question will be addressed by measuring the response of norepinephrine (NE) in cerebrospinal fluid (CSF) and plasma to the alpha-2 agonist clonidine. 2) Does the observed decrease in CSF agrinine vasopressin in AD reflect the cholinergic deficiency of AD? This questions will be addressed by measuring the response of AVP in CSF to the cholinesterase inhibitor physostigmine and to hypertonic saline. 3) Can the cholinergic deficiency of AD be documented in AD antemortem via blunted plasma neuroendocrine responses to increased CNS cholinergic stimulatory regulation (AVP, beta endorphin, NE, epinephrine and growth hormone) to physostigmine. These studies should increase knowledge of AD pathophysiology and suggest clinically useful diagnostic and therapeutic approaches to this disorder.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG008419-02
Application #
3120019
Study Section
Psychopathology and Clinical Biology Research Review Committee (PCB)
Project Start
1989-01-01
Project End
1991-12-31
Budget Start
1990-01-01
Budget End
1990-12-31
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Pan, Sheng; Zhu, David; Quinn, Joseph F et al. (2007) A combined dataset of human cerebrospinal fluid proteins identified by multi-dimensional chromatography and tandem mass spectrometry. Proteomics 7:469-73
Pan, Sheng; Wang, Yan; Quinn, Joseph F et al. (2006) Identification of glycoproteins in human cerebrospinal fluid with a complementary proteomic approach. J Proteome Res 5:2769-79
Li, Ge; Cherrier, Monique M; Tsuang, Debby W et al. (2006) Salivary cortisol and memory function in human aging. Neurobiol Aging 27:1705-14
Peskind, Elaine R; Li, Ge; Shofer, Jane et al. (2006) Age and apolipoprotein E*4 allele effects on cerebrospinal fluid beta-amyloid 42 in adults with normal cognition. Arch Neurol 63:936-9
Vuletic, Simona; Peskind, Elaine R; Marcovina, Santica M et al. (2005) Reduced CSF PLTP activity in Alzheimer's disease and other neurologic diseases; PLTP induces ApoE secretion in primary human astrocytes in vitro. J Neurosci Res 80:406-13
Peskind, Elaine R; Riekse, Robert; Quinn, Joseph F et al. (2005) Safety and acceptability of the research lumbar puncture. Alzheimer Dis Assoc Disord 19:220-5
Clark, Christopher M; Xie, Sharon; Chittams, Jesse et al. (2003) Cerebrospinal fluid tau and beta-amyloid: how well do these biomarkers reflect autopsy-confirmed dementia diagnoses? Arch Neurol 60:1696-702
Vuletic, Simona; Jin, Lee-Way; Marcovina, Santica M et al. (2003) Widespread distribution of PLTP in human CNS: evidence for PLTP synthesis by glia and neurons, and increased levels in Alzheimer's disease. J Lipid Res 44:1113-23
Petrie, E C; Peskind, E R; Dobie, D J et al. (2001) Plasma catecholamine and cardiovascular responses to physostigmine in Alzheimer's disease and aging. Psychoneuroendocrinology 26:147-64
Peskind, E R; Griffin, W S; Akama, K T et al. (2001) Cerebrospinal fluid S100B is elevated in the earlier stages of Alzheimer's disease. Neurochem Int 39:409-13

Showing the most recent 10 out of 49 publications