Hippocampal nerve growth factor receptor immunoreactivity in patients with Alzheimer's and Parkinson's disease.
Using the monoclonal antibody, ME 20.4, against the p75 nerve growth factor (NGF) receptor, NGF receptor-like immunoreactivity has been identified in axonal processes innervating the human hippocampus, where previously a loss of reactivity has been reported in a preliminary study of Alzheimer's disease [10]. In an extended analysis of 15 cases of Alzheimer's disease, the number of NGF receptor positive fibres in the fimbria and alveus was generally decreased compared with age-matched normal groups, in presenile but not senile cases (differentiated by age of onset before or after 65 years). By contrast, in 5 demented Parkinson's disease cases (aged 61-86 years at death) immunohistochemically reactive fibres were consistently minimal or absent. This pattern of NGF receptor loss in the hippocampus most closely reflects the loss of basal forebrain cholinergic neurones, previously reported within the different clinical groups but not by biochemical measures of cholinergic function. It is concluded that even at moderately advanced stages of Alzheimer's disease with onset in the senium, axonal processes and NGF receptor mechanisms may be structurally intact in areas of cholinergic innervation from the basal forebrain, despite evidence of cholinergic dysfunction (decreased choline acetyltransferase (ChAT) and acetylcholinesterase), but that in presenile Alzheimer's and in demented Parkinson's disease cases the receptor declines in conjunction with the loss of subcortical neurones and their processes. The loss of ChAT activity may therefore reflect a dysfunction of the NGF system, in its normal maintenance of the cholinergic phenotype in basal forebrain neurones.
Kerwin
J M
JM
MRC Neurochemical Pathology Unit, Newcastle General Hospital, UK.
Morris
C M
CM
Perry
R H
RH
Perry
E K
EK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000032:analysis; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006624:Hippocampus / Q000737:chemistry*; D006801:Humans; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000032:analysis*; D010300:Parkinson Disease / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000032:analysis*
D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D002795:Choline O-Acetyltransferase