Nerve growth factor receptor and choline acetyltransferase remain colocalized in the nucleus basalis (Ch4) of Alzheimer's patients

Jeffrey H. Kordower, Don M. Gash, Mark Bothwell, Louis Hersh, Elliott J. Mufson

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Previous investigations have demonstrated an almost exclusive "coupling" between the receptor for nerve growth factor and cholinergic neurons within the basal forebrain. The present series of experiments were carried out to address two questions. First, what is the status of nerve growth factor receptor-containing neurons within the basal forebrain of patients with histopathologically confirmed diagnoses of Alzheimer's disease (AD)? More importantly, the second experiment assesses the degree to which the receptor for nerve growth factor and choline acetyltransferase remain colocalized within AD basal forebrain. A "decoupling" of this relationship, in which nerve growth factor receptors are no longer present upon magnocellular cholinergic neurons, would suggest that a loss of trophic support is functionally antecedent to the neuronal shrinkage and neuronal death seen in the basal forebrain in AD. Data obtained from six AD cases and four normal controls demonstrated an extensive reduction in number and shrinkage in size of nerve growth factor receptor containing neurons within the Ch4 region of the basal forebrain. Double label studies using either immunofluorescence or immunoperoxidase techniques demonstrated that the receptor for nerve growth factor and choline acetyltransferase remain colocalized in AD patients. This was true for neurons exhibiting either healthy or dystrophic morphological profiles. These data confirm previous studies, demonstrating that both a loss and shrinkage of cholinergic neurons occurs within the AD basal forebrain. The results of the present immunohistochemical investigation suggest that the degenerative changes associated with these neurons do not result from impaired trophic support related to a loss of NGF receptors. However, the presence of NGF receptors on remaining cholinergic basal forebrain neurons in AD patients suggests that these neurons would still be responsive to NGF administration.

Original languageEnglish (US)
Pages (from-to)67-74
Number of pages8
JournalNeurobiology of Aging
Volume10
Issue number1
DOIs
StatePublished - 1989
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Choline acetyltransferase
  • Colocalization
  • Immunofluorescence
  • Immunoperoxidase
  • Nerve growth factor receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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