Impaired phosphoinositide hydrolysis in Alzheimer's disease brain

Richard S. Jope, Ling Song, Xiaohua Li, Richard Powers

Research output: Contribution to journalArticle

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Abstract

The effect of Alzheimer's disease (AD) on the activity of the phosphoinositide second messenger system was studied by measuring the hydrolysis of [3H]phosphatidylinositol (PI) by membranes from postmortem human prefrontal cortex. The activity of phospholipase C was similar in AD and control tissue. Activation with GTPγS and with carbachol demonstrated less [3H]PI hydrolysis in AD than control membranes. The concentration of Gq/11, the G-proteins most likely functional in phosphoinositide metabolism, was unchanged in AD compared with controls, indicating that function of the receptor-G-protein complex rather than the G-protein concentration was the site of the impairment in AD. These results indicate that postsynaptic muscarinic receptor responses are impaired in AD, a finding that may explain, in part, the limited therapeutic responses achieved by administration of cholinomimetics to patients with AD. Also, this assay provides a means to identify cholinomimetics that are most effective in activating muscarinic receptor-coupled phosphoinositide hydrolysis in human brain, agents which should have the greatest potential for providing therapeutic responses in AD.

Original languageEnglish (US)
Pages (from-to)221-226
Number of pages6
JournalNeurobiology of aging
Volume15
Issue number2
DOIs
StatePublished - Jan 1 1994

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Keywords

  • Alzheimer's disease
  • Cholinergic receptor
  • G-proteins
  • Human brain
  • Phosphoinositide hydrolysis

ASJC Scopus subject areas

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

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