Subtypes of Nicotinic Receptors in Human Cortex: Selective Changes in Alzheimer Disease

  • Kiminobu Sugaya
  • Ezio Giacobini
  • Vincent Chiappinelli
  • Robert Struble
Part of the Advances in Behavioral Biology book series (ABBI, volume 38A)

Abstract

Cholinergic deficits in Alzheimer disease (AD) have been well documented. Choline acetyltransferase (ChAt), the synthetic enzyme for acetylcholine (ACh), is consistently reduced by 50-95% in cortex and hippocampus of AD patients compared to age-matched controls (Bowen et al., 1976; Perry et al., 1978; Reisine et al., 1978; Davies, 1979; Zubenko et al., 1989). Reductions are also observed in high affinity choline uptake (HACU) (Rylett et al., 1983; Sims et al., 1983), in in vitro synthesis of ACh and release during depolarization (Blessed et al., 1968; Neary et al., 1986b), in presynaptic muscarinic and nicotinic receptor binding (Mash et al., 1985; Whitehouse, 1987; Kellar et al., 1987; Whitehouse et al., 1988; Giacobini et al., 1988a,b, 1989), in ACh and acetylcholinesterase (AChE) levels in cortex (Richter et al., 1980) and in cerebrospinal fluid (CSF) (Johns et al., 1983; Elble et al., 1987, 1989). The reduction of these presynaptic cholinergic markers is associated with a marked loss of cells in the nucleus basalis of Meynert which project to cortex (Whitehouse et al., 1982). By contrast, postsynaptic muscarinic receptor mechanisms appear to be relatively spared in AD patients (London and Coyle, 1978; Reisine et al., 1978; Davies, 1979; Giacobini et al., 1988a, 1989). The reductions of cortical and CSF cholinergic markers are closely correlated with the extent of neuropathology (senile plaques) and with the severity of cognitive impairment (Bowen et al., 1976; Perry et al., 1978; Fuld et al., 1982; Johns et al., 1983; Francis et al., 1985; Neary et al., 1986a; Elble et al., 1987). We have described changes in ACh and choline (Ch) metabolism in aging animals (Giacobini et al., 1987) and in the CSF of AD patients which may be related to neuronal membrane breakdown and reduced uptake of Ch by cholinergic neurons (Elble et al., 1989).

Keywords

Dopamine Dementia Nicotine Choline Acetylcholine 

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Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Kiminobu Sugaya
  • Ezio Giacobini
    • 1
  • Vincent Chiappinelli
    • 3
  • Robert Struble
    • 2
  1. 1.Depts. PharmacologySouthern Illinois University School of MedicineSpringfieldUSA
  2. 2.PsychiatrySouthern Illinois University School of MedicineSpringfieldUSA
  3. 3.Dept. PharmacologySt. Louis Univ.St. LouisUSA

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