Abstract

The objective of this study is to understand the reasons for the losses of enzymes of central cholinergic neurons in human aging, and in senile dementia of the Alzheimer type (SDAT). Using a specific antiserum against purified human choline acetyltransferase (ChAT), we will determine whether reductions in the activity of this enzyme are due to changes in its quality or in its quantity. We will search for antibodies to ChAT in autopsied brain tissue and in serum from cases of ADAT and in the normal elderly. We will assay ChAT, acetylcholinesterase (AChE), and concentrations of cholinergic receptors in the central nervous system of both normal individuals and cases of SDAT coming to autopsy. The results of these studies will be correlated with detailed psychological, morphometric, and pathologic data on the same cases. We will search for age-related changes in the enzymes and receptors of the cholinergic system in rat brain. If a decrement in ChAT activity is found, we will explore the quality and quantity of the enzyme molecules present, and will investigate rates of ChAT synthesis and degradation in young and old animals. We will attempt to reproduce some of the neurochemical features of SDAT in animals by chronic treatment with a specific inhibitor of the high affinity choline uptake system.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH038623-06
Application #
3376738
Study Section
Neurology A Study Section (NEUA)
Project Start
1983-04-01
Project End
1986-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Weinger, Jason G; Davies, Peter; Acker, Christopher M et al. (2012) Mice devoid of Tau have increased susceptibility to neuronal damage in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. J Neuropathol Exp Neurol 71:422-33
Boutajangout, Allal; Ingadottir, Johanna; Davies, Peter et al. (2011) Passive immunization targeting pathological phospho-tau protein in a mouse model reduces functional decline and clears tau aggregates from the brain. J Neurochem 118:658-67
Conejero-Goldberg, C; Hyde, T M; Chen, S et al. (2011) Molecular signatures in post-mortem brain tissue of younger individuals at high risk for Alzheimer's disease as based on APOE genotype. Mol Psychiatry 16:836-47
Momeni, Parastoo; DeTucci, Karen; Straub, Richard E et al. (2010) Progranulin (GRN) in two siblings of a Latino family and in other patients with schizophrenia. Neurocase 16:273-9
Rojo, Leonel E; Alzate-Morales, Jans; Saavedra, Ivan N et al. (2010) Selective interaction of lansoprazole and astemizole with tau polymers: potential new clinical use in diagnosis of Alzheimer's disease. J Alzheimers Dis 19:573-89
Tremblay, Matthew A; Acker, Christopher M; Davies, Peter (2009) Tau Phosphorylated at Tyrosine 394 is Found in Alzheimer's Disease Tangles and Can Be a Product of the Abl-Related Kinase, Arg. J Alzheimers Dis :
Davies, Peter; Koppel, Jeremy (2009) Mechanism-based treatments for Alzheimer's disease. Dialogues Clin Neurosci 11:159-69
Hu, Shuxin; Begum, Aynun N; Jones, Mychica R et al. (2009) GSK3 inhibitors show benefits in an Alzheimer's disease (AD) model of neurodegeneration but adverse effects in control animals. Neurobiol Dis 33:193-206
Rojo, Leonel E; Alzate-Morales, Jans; Saavedra, Ivan N et al. (2009) Selective Interaction of Lansoprazole and Astemizole with Tau Polymers: Potential New Clinical Use in Diagnosis of Alzheimer's Disease. J Alzheimers Dis :
Conejero-Goldberg, Concepcion; Townsend, Kirk; Davies, Peter (2008) Effects of cell cycle inhibitors on tau phosphorylation in N2aTau3R cells. J Mol Neurosci 35:143-50

Showing the most recent 10 out of 44 publications