Cholinergic activation of phosphoinositide signaling is impaired in Alzheimer's disease brain

Richard S Jope, Ling Song, Richard E. Powers

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

The function of the phosphoinositide signal transduction system was compared in membranes from Alzheimer's disease (AD) and control postmortem brain. [3H]Phosphatidylinositol hydrolysis was concentration-dependently stimulated by GTP[S] and this was 40% lower than controls in AD prefrontal cortical membranes. Carbachol induced a response greater than that of GTP[S] alone, and this response was impaired in AD by 45%. Differential analysis of the receptor-coupled and G-protein contributions to the responses indicated that the G-protein deficit in AD had a predominant influence on the lowered responses to cholinergic agonists. Similar deficits were observed in AD in the responses to five additional cholinergic agonists, including acetylcholine with three different acetylcholinesterase inhibitors. Deficits in stimulated phosphoinositide hydrolysis were regionally selective and these deficits did not correlate directly with reductions in choline acetyltransferase activity in AD tissues. These data demonstrate that in AD there is a brain region-selective, large impairment of cholinergic agonist-induced signal transduction mediated by the phosphoinositide system, which we speculate may impact on amyloid precursor protein processing.

Original languageEnglish
Pages (from-to)111-120
Number of pages10
JournalNeurobiology of Aging
Volume18
Issue number1
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

Fingerprint

Phosphatidylinositols
Cholinergic Agents
Alzheimer Disease
Cholinergic Agonists
Brain
Guanosine Triphosphate
Signal Transduction
Hydrolysis
Choline O-Acetyltransferase
Membranes
Amyloid beta-Protein Precursor
Cholinesterase Inhibitors
Carbachol
G-Protein-Coupled Receptors
GTP-Binding Proteins
Acetylcholine

Keywords

  • Alzheimer's disease
  • cholinergic
  • G-protein
  • muscarinic stimulation
  • phosphatidylinositol
  • phosphoinositide hydrolysis

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

Cite this

Cholinergic activation of phosphoinositide signaling is impaired in Alzheimer's disease brain. / Jope, Richard S; Song, Ling; Powers, Richard E.

In: Neurobiology of Aging, Vol. 18, No. 1, 01.01.1997, p. 111-120.

Research output: Contribution to journalArticle

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