Nerve growth factor receptor and choline acetyltransferase remain colocalized in the nucleus basalis (Ch4) of Alzheimer's patients.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Kordower
J H
JH
Department of Anatomy and Cell Biology, University of Illinois Medical Center 60612.
Gash
D M
DM
Bothwell
M
M
Hersh
L
L
Mufson
E J
EJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism*; D001479:Basal Ganglia / Q000032:analysis*; D002795:Choline O-Acetyltransferase / Q000032:analysis*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D009414:Nerve Growth Factors / Q000032:analysis*; D011956:Receptors, Cell Surface / Q000032:analysis*; D017475:Receptors, Nerve Growth Factor; D013377:Substantia Innominata / Q000032:analysis*
D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D002795:Choline O-Acetyltransferase